REFERENCES
1. Isakoff MS, Bielack SS, Meltzer P, Gorlick R. Osteosarcoma: current treatment and a collaborative pathway to success. J Clin Oncol. 2015;33:3029-35.
2. Gianferante DM, Mirabello L, Savage SA. Germline and somatic genetics of osteosarcoma - connecting aetiology, biology and therapy. Nat Rev Endocrinol. 2017;13:480-91.
3. Valery PC, Laversanne M, Bray F. Bone cancer incidence by morphological subtype: a global assessment. Cancer Causes Control. 2015;26:1127-39.
5. Chang JL, Wang WY, Li YM, et al. Chinese herbal medicine for osteosarcoma in the mouse: a systematic review and meta-analysis. Chin J Integr Med. 2019;25:370-7.
6. Tsuchiya T, Sekine K, Hinohara S, Namiki T, Nobori T, Kaneko Y. Analysis of the p16INK4, p14ARF, p15, TP53, and MDM2 genes and their prognostic implications in osteosarcoma and Ewing sarcoma. Cancer Genet Cytogenet. 2000;120:91-8.
7. Gonzalez KD, Noltner KA, Buzin CH, et al. Beyond Li Fraumeni Syndrome: clinical characteristics of families with p53 germline mutations. J Clin Oncol. 2009;27:1250-6.
8. Seidinger AL, Mastellaro MJ, Paschoal Fortes F, et al. Association of the highly prevalent TP53 R337H mutation with pediatric choroid plexus carcinoma and osteosarcoma in southeast Brazil. Cancer. 2011;117:2228-35.
9. Shimizu T, Sugihara E, Takeshima H, et al. Depletion of R270C mutant p53 in osteosarcoma attenuates cell growth but does not prevent invasion and metastasis in vivo. Cells. 2022;11:3614.
10. Mirabello L, Yeager M, Mai PL, et al. Germline TP53 variants and susceptibility to osteosarcoma. J Natl Cancer Inst. 2015;107:djv101.
11. Chen X, Bahrami A, Pappo A, et al; St. Jude Children’s Research Hospital-Washington University Pediatric Cancer Genome Project. Recurrent somatic structural variations contribute to tumorigenesis in pediatric osteosarcoma. Cell Rep. 2014;7:104-12.
12. Liu S, Yue J, Du W, Han J, Zhang W. LAMP3 plays an oncogenic role in osteosarcoma cells partially by inhibiting TP53. Cell Mol Biol Lett. 2018;23:33.
13. Chen YQ, Yang TQ, Zhou B, Yang MX, Feng HJ, Wang YL. HOXA5 overexpression promotes osteosarcoma cell apoptosis through the p53 and p38α MAPK pathway. Gene. 2019;689:18-23.
14. Samsa WE, Mamidi MK, Bashur LA, et al. The crucial p53-dependent oncogenic role of JAB1 in osteosarcoma in vivo. Oncogene. 2020;39:4581-91.
15. Li KW, Wang SH, Wei X, Hou YZ, Li ZH. Mechanism of miR-122-5p regulating the activation of PI3K-Akt-mTOR signaling pathway on the cell proliferation and apoptosis of osteosarcoma cells through targeting TP53 gene. Eur Rev Med Pharmacol Sci. 2020;24:12655-66.
16. Wan J, Long F, Zhang C, Liu Y. miR181bp53 negative feedback axis regulates osteosarcoma cell proliferation and invasion. Int J Mol Med. 2020;45:1803-13.
17. Otani S, Date Y, Ueno T, et al. Runx3 is required for oncogenic Myc upregulation in p53-deficient osteosarcoma. Oncogene. 2022;41:683-91.
18. Zoumpoulidou G, Alvarez-Mendoza C, Mancusi C, et al. Therapeutic vulnerability to PARP1,2 inhibition in RB1-mutant osteosarcoma. Nat Commun. 2021;12:7064.
19. van Harn T, Foijer F, van Vugt M, et al. Loss of Rb proteins causes genomic instability in the absence of mitogenic signaling. Genes Dev. 2010;24:1377-88.
20. Ballatori SE, Hinds PW. Osteosarcoma: prognosis plateau warrants retinoblastoma pathway targeted therapy. Signal Transduct Target Ther. 2016;1:16001.
21. Li Y, Yang S, Liu Y, Yang S. Deletion of Trp53 and Rb1 in Ctsk-expressing cells drives osteosarcoma progression by activating glucose metabolism and YAP signaling. MedComm. 2022;3:e131.
22. Li Y, Yang S, Yang S. Verteporfin inhibits the progression of spontaneous osteosarcoma caused by Trp53 and Rb1 deficiency in ctsk-expressing cells via impeding hippo pathway. Cells. 2022;11:1361.
23. Ren W, Gu G. Prognostic implications of RB1 tumour suppressor gene alterations in the clinical outcome of human osteosarcoma: a meta-analysis. Eur J Cancer Care. 2017;26:e12401.
24. Mohseny AB, Tieken C, van der Velden PA, et al. Small deletions but not methylation underlie CDKN2A/p16 loss of expression in conventional osteosarcoma. Genes Chromosomes Cancer. 2010;49:1095-103.
25. Letko A, Minor KM, Norton EM, et al. Genome-wide analyses for osteosarcoma in leonberger dogs reveal the CDKN2A/B gene locus as a major risk locus. Genes. 2021;12:1964.
26. Jiang J, Zhan X, Wei J, et al. Artificial intelligence reveals dysregulation of osteosarcoma and cuproptosis-related biomarkers, PDHA1, CDKN2A and neutrophils. Sci Rep. 2023;13:4927.
27. Shaikh AB, Li F, Li M, et al. Present advances and future perspectives of molecular targeted therapy for osteosarcoma. Int J Mol Sci. 2016;17:506.
29. Walz S, Lorenzin F, Morton J, et al. Activation and repression by oncogenic MYC shape tumour-specific gene expression profiles. Nature. 2014;511:483-7.
30. Yu W, Tang L, Lin F, Yao Y, Shen Z. DGKZ acts as a potential oncogene in osteosarcoma proliferation through its possible interaction with ERK1/2 and MYC pathway. Front Oncol. 2018;8:655.
31. Tang Y, Ji F. lncRNA HOTTIP facilitates osteosarcoma cell migration, invasion and epithelial-mesenchymal transition by forming a positive feedback loop with c-Myc. Oncol Lett. 2019;18:1649-56.
32. Gao J, Ma S, Yang F, et al. miR193b exhibits mutual interaction with MYC, and suppresses growth and metastasis of osteosarcoma. Oncol Rep. 2020;44:139-55.
33. Nirala BK, Patel TD, Kurenbekova L, et al. MYC regulates CSF1 expression via microRNA 17/20a to modulate tumor-associated macrophages in osteosarcoma. JCI Insight. 2023;8:e164947.
34. Ueno T, Otani S, Date Y, et al. Myc upregulates Ggct, γ-glutamylcyclotransferase to promote development of p53-deficient osteosarcoma. Cancer Sci. 2024;115:2961-71.
35. Wen J, Xie Y, Zhang Y, et al. MACC1 Contributes to the development of osteosarcoma through regulation of the HGF/c-Met pathway and microtubule stability. Front Cell Dev Biol. 2020;8:825.
36. Kawano M, Tanaka K, Itonaga I, Iwasaki T, Kubota Y, Tsumura H. The anti-oncogenic effect of 17-DMAG via the inactivation of HSP90 and MET pathway in osteosarcoma cells. Oncol Res. 2023;31:631-43.
37. Patanè S, Avnet S, Coltella N, et al. MET overexpression turns human primary osteoblasts into osteosarcomas. Cancer Res. 2006;66:4750-7.
38. Lu KH, Yang JS, Hsieh YH, et al. Lipocalin-2 inhibits osteosarcoma cell metastasis by suppressing MET expression via the MEK-ERK pathway. Cancers. 2021;13:3181.
39. Jia T, Cai M, Wang Z, Chen T. Anticancer effect of crizotinib on osteosarcoma cells by targeting c-Met signaling pathway. Cell Mol Biol. 2023;69:174-8.
40. Fu X, Huang J, Chen X, et al. Development of dual aptamers-functionalized c-MET PROTAC degraders for targeted therapy of osteosarcoma. Theranostics. 2025;15:103-21.
41. Wang LL, Gannavarapu A, Kozinetz CA, et al. Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund-Thomson syndrome. J Natl Cancer Inst. 2003;95:669-74.
42. Ng AJ, Walia MK, Smeets MF, et al. The DNA helicase recql4 is required for normal osteoblast expansion and osteosarcoma formation. PLoS Genet. 2015;11:e1005160.
43. Miller CW, Aslo A, Won A, Tan M, Lampkin B, Koeffler HP. Alterations of the p53, Rb and MDM2 genes in osteosarcoma. J Cancer Res Clin Oncol. 1996;122:559-65.
44. Wang X, Wang S, Feng C. Detection of p53 and MDM2 gene expression in osteosarcoma with biotin-labelled in situ. Chin J Surg. 1997;35(3):178-180.
45. Xie C, Wu B, Chen B, et al. Histone deacetylase inhibitor sodium butyrate suppresses proliferation and promotes apoptosis in osteosarcoma cells by regulation of the MDM2-p53 signaling. Onco Targets Ther. 2016;9:4005-13.
46. Skalniak L, Twarda-Clapa A, Neochoritis CG, et al. A fluorinated indole-based MDM2 antagonist selectively inhibits the growth of p53wt osteosarcoma cells. FEBS J. 2019;286:1360-74.
48. Omori K, Otani S, Date Y, et al. C/ebpα represses the oncogenic Runx3-Myc axis in p53-deficient osteosarcoma development. Oncogene. 2023;42:2485-94.
49. Hou P, Ji M, Yang B, et al. Quantitative analysis of promoter hypermethylation in multiple genes in osteosarcoma. Cancer. 2006;106:1602-9.
50. Lopez C, Abuel-Haija M, Pena L, Coppola D. Novel germline PTEN mutation associated with cowden syndrome and osteosarcoma. Cancer Genomics Proteomics. 2018;15:115-20.
51. Zhou J, Xiao X, Wang W, Luo Y. Association between PTEN and clinical-pathological features of osteosarcoma. Biosci Rep. 2019;39:BSR20190954.
52. Song D, Ni J, Xie H, Ding M, Wang J. DNA demethylation in the PTEN gene promoter induced by 5-azacytidine activates PTEN expression in the MG-63 human osteosarcoma cell line. Exp Ther Med. 2014;7:1071-6.
53. Zhang Y, Liu Z, Yang X, et al. H3K27 acetylation activated-COL6A1 promotes osteosarcoma lung metastasis by repressing STAT1 and activating pulmonary cancer-associated fibroblasts. Theranostics. 2021;11:1473-92.
54. Yang P, Liu Y, Qi YC, Lian ZH. High SENP3 expression promotes cell migration, invasion, and proliferation by modulating DNA methylation of E-cadherin in osteosarcoma. Technol Cancer Res Treat. 2020;19:1533033820956988.
55. Sun JM, Chow WY, Xu G, et al. The role of FAS receptor methylation in osteosarcoma metastasis. Int J Mol Sci. 2023;24:12155.
56. Wang Y, Qin N, Zhao C, et al. The correlation between the methylation of PTEN gene and the apoptosis of osteosarcoma cells mediated by SeHA nanoparticles. Colloids Surf B Biointerfaces. 2019;184:110499.
57. Kong D, Ying B, Zhang J, Ying H. PCAF regulates H3 phosphorylation and promotes autophagy in osteosarcoma cells. Biomed Pharmacother. 2019;118:109395.
58. Huang YZ, Zhang J, Shen JJ, Zhao TX, Xu YJ. miRNA-296-5p functions as a potential tumor suppressor in human osteosarcoma by targeting SND1. Chin Med J. 2021;134:564-72.
59. Abedi S, Behmanesh A, Mazhar FN, et al. Machine learning and experimental analyses identified miRNA expression models associated with metastatic osteosarcoma. Biochim Biophys Acta Mol Basis Dis. 2024;1870:167357.
60. Yang D, Chen Y, He ZNT, et al. Indoleamine 2,3-dioxygenase 1 promotes osteosarcoma progression by regulating tumor-derived exosomal miRNA hsa-miR-23a-3p. Front Pharmacol. 2023;14:1194094.
61. Shan HJ, Zhu LQ, Yao C, et al. MAFG-driven osteosarcoma cell progression is inhibited by a novel miRNA miR-4660. Mol Ther Nucleic Acids. 2021;24:385-402.
62. Luo P, Zhang YD, He F, et al. HIF-1α-mediated augmentation of miRNA-18b-5p facilitates proliferation and metastasis in osteosarcoma through attenuation PHF2. Sci Rep. 2022;12:10398.
63. Liu SH, Zhu JW, Xu HH, et al. A novel antisense long non-coding RNA SATB2-AS1 overexpresses in osteosarcoma and increases cell proliferation and growth. Mol Cell Biochem. 2017;430:47-56.
64. Li JP, Liu LH, Li J, et al. Microarray expression profile of long noncoding RNAs in human osteosarcoma. Biochem Biophys Res Commun. 2013;433:200-6.
65. Gong H, Tao Y, Xiao S, et al. LncRNA KIAA0087 suppresses the progression of osteosarcoma by mediating the SOCS1/JAK2/STAT3 signaling pathway. Exp Mol Med. 2023;55:831-43.
66. Pan X, Guo J, Liu C, et al. LncRNA HCG18 promotes osteosarcoma growth by enhanced aerobic glycolysis via the miR-365a-3p/PGK1 axis. Cell Mol Biol Lett. 2022;27:5.
67. Shen Y, Xu J, Pan X, et al. LncRNA KCNQ1OT1 sponges miR-34c-5p to promote osteosarcoma growth via ALDOA enhanced aerobic glycolysis. Cell Death Dis. 2020;11:278.
68. Yang D, Liu K, Fan L, et al. LncRNA RP11-361F15.2 promotes osteosarcoma tumorigenesis by inhibiting M2-Like polarization of tumor-associated macrophages of CPEB4. Cancer Lett. 2020;473:33-49.
69. Xie W, Ma F, Dou L, et al. Allicin affects immunoreactivity of osteosarcoma cells through lncRNA CBR3-AS1. Heliyon. 2024;10:e31971.
70. Tang N, Chen Y, Su Y, Zhang S, Huang T. The role of disulfidptosis-associated LncRNA-LINC01137 in osteosarcoma biology and its regulatory effects on macrophage polarization. Funct Integr Genomics. 2024;24:219.
71. Li R, Chen P, Zhou Y, et al. LncRNA HOXA-AS3 promotes cell proliferation and invasion via targeting miR-218-5p/FOXP1 axis in osteosarcoma. Sci Rep. 2024;14:16581.
72. Tao H, Chen F, Liu H, Hu Y, Wang Y, Li H. Wnt/β-catenin signaling pathway activation reverses gemcitabine resistance by attenuating Beclin1-mediated autophagy in the MG63 human osteosarcoma cell line. Mol Med Rep. 2017;16:1701-6.
73. Wang Q, Liu H, Wang Q, et al. Involvement of c-Fos in cell proliferation, migration, and invasion in osteosarcoma cells accompanied by altered expression of Wnt2 and Fzd9. PLoS One. 2017;12:e0180558.
74. Chen L, Zhou SJ, Xu Y, Liao QM, Zou YS, Pei H. CCAR2 promotes a malignant phenotype of osteosarcoma through Wnt/β-catenin-dependent transcriptional activation of SPARC. Biochem Biophys Res Commun. 2021;580:67-73.
75. Chen T, Chen Z, Lian X, et al. MUC 15 promotes osteosarcoma cell proliferation, migration and invasion through livin, MMP-2/MMP-9 and Wnt/β-catenin signal pathway. J Cancer. 2021;12:467-73.
76. Giatagana EM, Berdiaki A, Gaardløs M, Tsatsakis AM, Samsonov SA, Nikitovic D. Rapamycin-induced autophagy in osteosarcoma cells is mediated via the biglycan/Wnt/β-catenin signaling axis. Am J Physiol Cell Physiol. 2022;323:C1740-56.
77. Ji H, Kong L, Wang Y, et al. CD44 expression is correlated with osteosarcoma cell progression and immune infiltration and affects the Wnt/β-catenin signaling pathway. J Bone Oncol. 2023;41:100487.
78. Martins-Neves SR, Paiva-Oliveira DI, Wijers-Koster PM, et al. Chemotherapy induces stemness in osteosarcoma cells through activation of Wnt/β-catenin signaling. Cancer Lett. 2016;370:286-95.
79. Tran DTP, Kuchimaru T, Pongsuchart M, et al. ROR2 regulates the survival of murine osteosarcoma cells in lung capillaries. J Cancer Metastasis Treat. 2020:2020.
80. Lobry C, Oh P, Aifantis I. Oncogenic and tumor suppressor functions of Notch in cancer: it’s NOTCH what you think. J Exp Med. 2011;208:1931-5.
81. Qin J, Wang R, Zhao C, et al. Notch signaling regulates osteosarcoma proliferation and migration through Erk phosphorylation. Tissue Cell. 2019;59:51-61.
82. Cheng J, Zhang Y, Wan R, et al. CEMIP promotes osteosarcoma progression and metastasis through activating notch signaling pathway. Front Oncol. 2022;12:919108.
83. Liang G, Duan C, He J, Shi L. Spindle and kinetochore-related complex subunit 3 has a protumour function in osteosarcoma by activating the Notch pathway. Toxicol Appl Pharmacol. 2024;483:116826.
84. Zhang J, Li N, Lu S, et al. The role of Notch ligand Jagged1 in osteosarcoma proliferation, metastasis, and recurrence. J Orthop Surg Res. 2021;16:226.
85. Yun HM, Kim SH, Kwon YJ, Park KR. Effect of spicatoside a on anti-osteosarcoma MG63 cells through reactive oxygen species generation and the inhibition of the PI3K-AKT-mTOR pathway. Antioxidants. 2024;13:1162.
86. Huang X, Xia K, Wei Z, Liu W, Wei Z, Guo W. SLC38A5 suppresses ferroptosis through glutamine-mediated activation of the PI3K/AKT/mTOR signaling in osteosarcoma. J Transl Med. 2024;22:1004.
87. Jiang N, Wang X, Xie X, et al. lncRNA DANCR promotes tumor progression and cancer stemness features in osteosarcoma by upregulating AXL via miR-33a-5p inhibition. Cancer Lett. 2017;405:46-55.
88. Zhu J, Sun Y, Lu Y, et al. Glaucocalyxin a exerts anticancer effect on osteosarcoma by inhibiting GLI1 nuclear translocation via regulating PI3K/Akt pathway. Cell Death Dis. 2018;9:708.
89. Meng CY, Zhao ZQ, Bai R, et al. MicroRNA22 mediates the cisplatin resistance of osteosarcoma cells by inhibiting autophagy via the PI3K/Akt/mTOR pathway. Oncol Rep. 2020;43:1169-86.
90. Qiu C, Su W, Shen N, et al. MNAT1 promotes proliferation and the chemo-resistance of osteosarcoma cell to cisplatin through regulating PI3K/Akt/mTOR pathway. BMC Cancer. 2020;20:1187.
91. Chen Z, Ni R, Hu Y, Yang Y, Tian Y. Arnicolide D inhibits proliferation and induces apoptosis of osteosarcoma cells through PI3K/Akt/mTOR pathway. Anticancer Agents Med Chem. 2024;24:1288-94.
92. Jing D, Wu W, Chen X, et al. Quercetin encapsulated in folic acid-modified liposomes is therapeutic against osteosarcoma by non-covalent binding to the JH2 domain of JAK2 Via the JAK2-STAT3-PDL1. Pharmacol Res. 2022;182:106287.
93. Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149:1060-72.
94. Liu Q, Wang K. The induction of ferroptosis by impairing STAT3/Nrf2/GPx4 signaling enhances the sensitivity of osteosarcoma cells to cisplatin. Cell Biol Int. 2019;43:1245-56.
95. Chen W, Li Z, Yu N, et al. Bone-targeting exosome nanoparticles activate Keap1 / Nrf2 / GPX4 signaling pathway to induce ferroptosis in osteosarcoma cells. J Nanobiotechnology. 2023;21:355.
96. Yuan C, Fan R, Zhu K, Wang Y, Xie W, Liang Y. Curcumin induces ferroptosis and apoptosis in osteosarcoma cells by regulating Nrf2/GPX4 signaling pathway. Exp Biol Med. 2023;248:2183-97.
97. Li Y, Bai X. Naringenin induces ferroptosis in osteosarcoma cells through the STAT3-MGST2 signaling pathway. J Bone Oncol. 2025;50:100657.
98. Shao Y, Zuo X. PTPRC inhibits ferroptosis of osteosarcoma cells via blocking TFEB/FTH1 signaling. Mol Biotechnol. 2024;66:2985-94.
99. Cersosimo F, Lonardi S, Bernardini G, et al. Tumor-associated macrophages in osteosarcoma: from mechanisms to therapy. Int J Mol Sci. 2020;21:5207.
100. Li Y, Li M, Wei R, Wu J. Identification and functional analysis of EPOR+ tumor-associated macrophages in human osteosarcoma lung metastasis. J Immunol Res 2020;2020:9374240.[PMID:32908942 DOI:10.1155/2020/9374240 PMCID:PMC7450330] Caution!.
101. Wang J, Jin J, Chen T, Zhou Q. Curcumol synergizes with cisplatin in osteosarcoma by inhibiting M2-like polarization of tumor-associated macrophages. Molecules. 2022;27:4345.
102. Guo Z, Saw PE, Jon S. Non-invasive physical stimulation to modulate the tumor microenvironment: unveiling a new frontier in cancer therapy. BIO Integr. 2024;5:1-14.
103. Yan CF, Xia J, Qun WS, et al. Tumor-associated macrophages-derived exo-let-7a promotes osteosarcoma metastasis via targeting C15orf41 in osteosarcoma. Environ Toxicol. 2023;38:1318-31.
104. Tatsuno R, Ichikawa J, Komohara Y, et al. Pivotal role of IL-8 derived from the interaction between osteosarcoma and tumor-associated macrophages in osteosarcoma growth and metastasis via the FAK pathway. Cell Death Dis. 2024;15:108.
105. Hashimoto K, Nishimura S, Akagi M. Characterization of PD-1/PD-L1 immune checkpoint expression in osteosarcoma. Diagnostics. 2020;10:528.
106. Wang J, Zhang H, Sun X, et al. Exosomal PD-L1 and N-cadherin predict pulmonary metastasis progression for osteosarcoma patients. J Nanobiotechnology. 2020;18:151.
107. Toda Y, Kohashi K, Yamada Y, et al. PD-L1 and IDO1 expression and tumor-infiltrating lymphocytes in osteosarcoma patients: comparative study of primary and metastatic lesions. J Cancer Res Clin Oncol. 2020;146:2607-20.
108. Shi C, Huang CM, Wang B, Sun TF, Zhu AX, Zhu YC. Pseudogene MSTO2P enhances hypoxia-induced osteosarcoma malignancy by upregulating PD-L1. Biochem Biophys Res Commun. 2020;530:673-9.
109. Zheng S, Wei Y, Jiang Y, Hao Y. LRP8 activates STAT3 to induce PD-L1 expression in osteosarcoma. Tumori. 2021;107:238-46.
110. Lin J, Xu A, Jin J, et al. MerTK-mediated efferocytosis promotes immune tolerance and tumor progression in osteosarcoma through enhancing M2 polarization and PD-L1 expression. Oncoimmunology. 2022;11:2024941.
111. Wu H, Zhang J, Dai R, Xu J, Feng H. Transferrin receptor-1 and VEGF are prognostic factors for osteosarcoma. J Orthop Surg Res. 2019;14:296.
112. Al-Khalaf HH, Aboussekhra A. AUF1 positively controls angiogenesis through mRNA stabilization-dependent up-regulation of HIF-1α and VEGF-A in human osteosarcoma. Oncotarget. 2019;10:4868-79.
113. Xue M, Shen J, Cui J, et al. MicroRNA-638 expression change in osteosarcoma patients via PLD1 and VEGF expression. Exp Ther Med 2019;17:3899-906.[PMID:30988774 DOI:10.3892/etm.2019.7429 PMCID:PMC6447936] Caution!.
114. Ji X, Shan L, Shen P, He M. Circular RNA circ_001621 promotes osteosarcoma cells proliferation and migration by sponging miR-578 and regulating VEGF expression. Cell Death Dis. 2020;11:18.
115. Kaławaj K, Sławińska-Brych A, Mizerska-Kowalska M, et al. Alpha ketoglutarate exerts in vitro anti-osteosarcoma effects through inhibition of cell proliferation, induction of apoptosis via the JNK and caspase 9-dependent mechanism, and suppression of TGF-β and VEGF production and metastatic potential of cells. Int J Mol Sci. 2020;21:9406.
116. Jubelin C, Muñoz-Garcia J, Cochonneau D, Moranton E, Heymann MF, Heymann D. Biological evidence of cancer stem-like cells and recurrent disease in osteosarcoma. Cancer Drug Resist. 2022;5:184-98.
117. Li J, Zhong XY, Li ZY, et al. CD133 expression in osteosarcoma and derivation of CD133+ cells. Mol Med Rep. 2013;7:577-84.
118. Li K, Li X, Tian J, Wang H, Pan J, Li J. Downregulation of DNA-PKcs suppresses P-gp expression via inhibition of the Akt/NF-κB pathway in CD133-positive osteosarcoma MG-63 cells. Oncol Rep. 2016;36:1973-80.
119. Wang JH, Gong C, Guo FJ, et al. Knockdown of STIP1 inhibits the invasion of CD133positive cancer stemlike cells of the osteosarcoma MG63 cell line via the PI3K/Akt and ERK1/2 pathways. Int J Mol Med. 2020;46:2251-9.
120. Xu N, Kang Y, Wang W, Zhou J. The prognostic role of CD133 expression in patients with osteosarcoma. Clin Exp Med. 2020;20:261-7.
121. He A, Yang X, Huang Y, et al. CD133+ CD44+ cells mediate in the lung metastasis of osteosarcoma. J Cell Biochem. 2015;116:1719-29.
122. Shiratori H, Koshino T, Uesugi M, Nitto H, Saito T. Acceleration of lung metastasis by up-regulation of CD44 expression in osteosarcoma-derived cell transplanted mice. Cancer Lett. 2001;170:177-82.
123. Kim CK, Oh S, Kim SJ, Leem SH, Heo J, Chung SH. Correlation of IGF1R expression with ABCG2 and CD44 expressions in human osteosarcoma. Genes Genomics. 2018;40:381-8.
124. Gerardo-Ramírez M, Keggenhoff FL, Giam V, et al. CD44 contributes to the regulation of MDR1 protein and doxorubicin chemoresistance in osteosarcoma. Int J Mol Sci. 2022;23:8616.
125. Wang B, Hu H, Wang X, et al. POLE2 promotes osteosarcoma progression by enhancing the stability of CD44. Cell Death Discov. 2024;10:177.
126. Cortini M, Massa A, Avnet S, Bonuccelli G, Baldini N. Tumor-activated mesenchymal stromal cells promote osteosarcoma stemness and migratory potential via IL-6 secretion. PLoS One. 2016;11:e0166500.
127. Li Z, Wang Y, Hu R, Xu R, Xu W. LncRNA B4GALT1-AS1 recruits HuR to promote osteosarcoma cells stemness and migration via enhancing YAP transcriptional activity. Cell Prolif. 2018;51:e12504.
128. Yang Z, Liu Z, Lu W, Guo H, Chen J, Zhang Y. LncRNA WAC-AS1 promotes osteosarcoma Metastasis and stemness by sponging miR-5047 to upregulate SOX2. Biol Direct. 2023;18:74.
129. Liu F, Li L, Li Y, et al. Overexpression of SENP1 reduces the stemness capacity of osteosarcoma stem cells and increases their sensitivity to HSVtk/GCV. Int J Oncol. 2018;53:2010-20.
130. Chen Y, Wang T, Huang M, et al. MAFB promotes cancer stemness and tumorigenesis in osteosarcoma through a Sox9-mediated positive feedback loop. Cancer Res. 2020;80:2472-83.
131. Wei Z, Zheng D, Xia K, et al. DUSP3 restrains the progression and stemness property of osteosarcoma through regulating EGFR/STAT3/SOX2 axis. Int J Biol Sci. 2025;21:160-74.
132. Adel N. Overview of chemotherapy-induced nausea and vomiting and evidence-based therapies. Am J Manag Care. 2017;23(14 Suppl):S259-S265.
133. Zeng J, Wu Q, Meng XD, Wang J. Systematic review of Buzhong Yiqi method in alleviating cancer-related fatigue: a meta-analysis and exploratory network pharmacology approach. Front Pharmacol. 2024;15:1451773.
134. Morishige KI. Traditional herbal medicine, Rikkunshito, for chemotherapy-induced nausea and vomiting. J Gynecol Oncol. 2017;28:e57.
135. Duan X, Pan L, Bao Q, Peng D. UPLC-Q-TOF-MS study of the mechanism of THSWD for breast cancer treatment. Front Pharmacol. 2019;10:1625.
136. Huang J, Guo W, Cheung F, Tan HY, Wang N, Feng Y. Integrating network pharmacology and experimental models to investigate the efficacy of coptidis and scutellaria containing huanglian jiedu decoction on hepatocellular carcinoma. Am J Chin Med. 2020;48:161-82.
137. Hosseini A, Razavi BM, Banach M, Hosseinzadeh H. Quercetin and metabolic syndrome: a review. Phytother Res. 2021;35:5352-64.
138. Georgiou N, Kakava MG, Routsi EA, et al. Quercetin: a potential polydynamic drug. Molecules. 2023;28:8141.
139. Alizadeh SR, Ebrahimzadeh MA. Quercetin derivatives: drug design, development, and biological activities, a review. Eur J Med Chem. 2022;229:114068.
140. Chen YQ, Yang D, Li K, Liu JS, Feng HJ, Zhou JW. Thermo-responsive nano-hydrogel-based delivery of Saikosaponin a to enhance anti-PD-1 therapy in osteosarcoma. Nanomedicine. 2025;20:1677-91.
141. Wang W, Li M, Wang L, Chen L, Goh BC. Curcumin in cancer therapy: exploring molecular mechanisms and overcoming clinical challenges. Cancer Lett. 2023;570:216332.
142. Xu C, Wang M, Zandieh Doulabi B, Sun Y, Liu Y. Paradox: curcumin, a natural antioxidant, suppresses osteosarcoma cells via excessive reactive oxygen species. Int J Mol Sci. 2023;24:11975.
143. Huang C, Lu HF, Chen YH, Chen JC, Chou WH, Huang HC. Curcumin, demethoxycurcumin, and bisdemethoxycurcumin induced caspase-dependent and -independent apoptosis via Smad or Akt signaling pathways in HOS cells. BMC Complement Med Ther. 2020;20:68.
144. Wen L, Chan BC, Qiu MH, Leung PC, Wong CK. Artemisinin and its derivatives as potential anticancer agents. Molecules. 2024;29:3886.
145. Li Z, Ding X, Wu H, Liu C. Artemisinin inhibits angiogenesis by regulating p38 MAPK/CREB/TSP-1 signaling pathway in osteosarcoma. J Cell Biochem. 2019;120:11462-70.
146. Jing D, Chen X, Zhang Z, et al. 2-Hydroxy-3-methylanthraquinone inhibits homologous recombination repair in osteosarcoma through the MYC-CHK1-RAD51 axis. Mol Med. 2023;29:15.
147. Hu T, Fei Z, Wei N. Chemosensitive effects of Astragaloside IV in osteosarcoma cells via induction of apoptosis and regulation of caspase-dependent Fas/FasL signaling. Pharmacol Rep. 2017;69:1159-64.
148. Wen RJ, Dong X, Zhuang HW, et al. Baicalin induces ferroptosis in osteosarcomas through a novel Nrf2/xCT/GPX4 regulatory axis. Phytomedicine. 2023;116:154881.
149. Zhang Z, Yu C, Wang H, et al. The history, beneficial ingredients, mechanism, processing, and products of Panax ginseng for medicinal and edible value. Food Med Homol. 2025.
150. Liu MY, Jiang DX, Zhao X, et al. Exploration in the mechanism of ginsenoside Rg5 for the treatment of osteosarcoma by network pharmacology and molecular docking. Orthop Surg. 2024;16:462-70.
151. Li HY, Zhang J, Sun LL, et al. Celastrol induces apoptosis and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells: an in vitro and in vivo study. Cell Death Dis. 2015;6:e1604.
152. Ni Y, Zhu Y, Xu L, Duan J, Xiao P. Pharmacological activities and mechanisms of proteins and peptides derived from traditional Chinese medicine. Sci Tradit Chin Med. 2024;2:260-75.
153. Zhao Z, Wu Q, Xu Y, et al. Groenlandicine enhances cisplatin sensitivity in cisplatin-resistant osteosarcoma cells through the BAX/Bcl-2/Caspase-9/Caspase-3 pathway. J Bone Oncol. 2024;48:100631.
154. Zhao W, Chen Z, Guan M. Polydatin enhances the chemosensitivity of osteosarcoma cells to paclitaxel. J Cell Biochem. 2019;120:17481-90.
155. Wang ZD, Wang RZ, Xia YZ, Kong LY, Yang L. Reversal of multidrug resistance by icaritin in doxorubicin-resistant human osteosarcoma cells. Chin J Nat Med. 2018;16:20-8.
156. Lu M, Xie K, Lu X, Lu L, Shi Y, Tang Y. Notoginsenoside R1 counteracts mesenchymal stem cell-evoked oncogenesis and doxorubicin resistance in osteosarcoma cells by blocking IL-6 secretion-induced JAK2/STAT3 signaling. Invest New Drugs. 2021;39:416-25.
157. Xie C, Sun Q, Chen J, et al. Cu-Tremella fuciformis polysaccharide-based tumor microenvironment-responsive injectable gels for cuproptosis-based synergistic osteosarcoma therapy. Int J Biol Macromol. 2024;270:132029.
158. Lu S, Li Y, Yu Y. Glutathione-scavenging celastrol-Cu nanoparticles induce self-amplified cuproptosis for augmented cancer immunotherapy. Adv Mater. 2024;36:2404971.
159. Niu Y, Stadler FJ, He T, Zhang X, Yu Y, Chen S. Smart multifunctional polyurethane microcapsules for the quick release of anticancer drugs in BGC 823 and HeLa tumor cells. J Mater Chem B. 2017;5:9477-81.
160. Yi X, Wang F, Feng Y, Zhu J, Wu Y. Danhong injection attenuates doxorubicin-induced cardiotoxicity in rats via suppression of apoptosis: network pharmacology analysis and experimental validation. Front Pharmacol. 2022;13:929302.
161. Shen J, Zhang M, Zhang K, et al. Effect of angelica polysaccharide on mouse myeloid-derived suppressor cells. Front Immunol. 2022;13:989230.
162. Fu L, Zhang W, Zhou X, Fu J, He C. Tumor cell membrane-camouflaged responsive nanoparticles enable MRI-guided immuno-chemodynamic therapy of orthotopic osteosarcoma. Bioact Mater. 2022;17:221-33.
163. Ding X, Zhang Y, Liang J, et al. Dihydroartemisinin potentiates VEGFR-TKIs antitumorigenic effect on osteosarcoma by regulating Loxl2/VEGFA expression and lipid metabolism pathway. J Cancer. 2023;14:809-20.
164. Zhang X, Chen H, Zhang Y, et al. HA-DOPE-modified honokiol-loaded liposomes targeted therapy for osteosarcoma. Int J Nanomedicine. 2022;17:5137-51.
165. Yu T, Cai Z, Chang X, et al. Research progress of nanomaterials in chemotherapy of osteosarcoma. Orthop Surg. 2023;15:2244-59.
166. Shen M, Wang Y, Bing T, Tang Y, Liu X, Yu Y. Alendronate triggered dual-cascade targeting prodrug nanoparticles for enhanced tumor penetration and STING activation of osteosarcoma. Adv Funct Mater. 2023;33:2307013.
167. Zhang Y, You P, Liu R, et al. Artificial intelligence in clinical trials of lung cancer: current and future prospects. Intell Oncol. 2025;1:34-51.
168. Wang Y, Zhang Q, Chen Y, et al. Antitumor effects of immunity-enhancing traditional Chinese medicine. Biomed Pharmacother. 2020;121:109570.
169. Yang J, Wahner-Roedler DL, Zhou X, et al. Acupuncture for palliative cancer pain management: systematic review. BMJ Support Palliat Care. 2021;11:264-70.
170. He Y, Guo X, May BH, et al. Clinical evidence for association of acupuncture and acupressure with improved cancer pain: a systematic review and meta-analysis. JAMA Oncol. 2020;6:271-8.
171. Yan Y, López-Alcalde J, Zhang L, Siebenhüner AR, Witt CM, Barth J. Acupuncture for the prevention of chemotherapy-induced nausea and vomiting in cancer patients: a systematic review and meta-analysis. Cancer Med. 2023;12:12504-17.
172. Wang M, Liu W, Ge J, Liu S. The immunomodulatory mechanisms for acupuncture practice. Front Immunol. 2023;14:1147718.
173. Xu X, Feng X, He M, et al. The effect of acupuncture on tumor growth and gut microbiota in mice inoculated with osteosarcoma cells. Chin Med. 2020;15:33.
174. Wang N, Zhao L, Zhang D, Kong F. Research progress on the immunomodulatory mechanism of acupuncture in tumor immune microenvironment. Front Immunol. 2023;14:1092402.
175. Xiang Y, Yang Y, Liu J, Yang X. Functional role of MicroRNA/PI3K/AKT axis in osteosarcoma. Front Oncol. 2023;13:1219211.
176. Ma YS, Peng SF, Wu RS, et al. Bisdemethoxycurcumin suppresses human osteosarcoma U2 OS cell migration and invasion via affecting the PI3K/Akt/NFκB, PI3K/Akt/GSK3β and MAPK signaling pathways in vitro. Oncol Rep. 2022;48:210.
177. Zhang L, Yang C, Huang Y, et al. Cardamonin inhibits the growth of human osteosarcoma cells through activating P38 and JNK signaling pathway. Biomed Pharmacother. 2021;134:111155.
178. Jiwa H, Xie Z, Qu X, et al. Casticin induces ferroptosis in human osteosarcoma cells through Fe2+ overload and ROS production mediated by HMOX1 and LC3-NCOA4. Biochem Pharmacol. 2024;226:116346.
179. Vundavilli H, Datta A, Sima C, et al. Anti-tumor effects of cryptotanshinone (C19H20O3) in human osteosarcoma cell lines. Biomed Pharmacother. 2022;150:112993.
180. Huang X, Zeng J, Ruan S, Lei Z, Zhang J, Cao H. The use of matrine to inhibit osteosarcoma cell proliferation via the regulation of the MAPK/ERK signaling pathway. Front Oncol. 2024;14:1338811.
181. Xu X, Liu M, Wu H. Berberine inhibits the growth of osteosarcoma through modulating MMP/NM-23 and MAPK/JNK signal pathways. Am J Transl Res. 2023;15:729-44.
182. Gao X, Zhang C, Wang Y, Zhang P, Zhang J, Hong T. Berberine and cisplatin exhibit synergistic anticancer effects on osteosarcoma MG-63 cells by inhibiting the MAPK pathway. Molecules. 2021;26:1666.
183. Wang W, Li J, Ding Z, et al. Tanshinone I inhibits the growth and metastasis of osteosarcoma via suppressing JAK/STAT3 signalling pathway. J Cell Mol Med. 2019;23:6454-65.
184. Cai Q, Zhang W, Sun Y, et al. Study on the mechanism of andrographolide activation. Front Neurosci. 2022;16:977376.
185. Annamalai V, Kotakonda M, Periyannan V. JAK1/STAT3 regulatory effect of β-caryophyllene on MG-63 osteosarcoma cells via ROS-induced apoptotic mitochondrial pathway by DNA fragmentation. J Biochem Mol Toxicol. 2020;34:e22514.
