polydatin enhances the chemosensitivity of osteosarcoma cells to paclitaxel despite improvements in the prognosis of osteosarcoma patients chemotherapy fails in a considerable number of cases due to drug resistance the development of novel agents may enhance chemosensitivity this study explored the anticancer function of polydatin and its abilityin combination with paclitaxelto overcome drug resistance in human osteosarcoma u2os and mg63 cell lines a cell proliferation assay celll counting kit8 a cellcycle assay an apoptosis assay annexin vfluorescein isothiocyanatepropidium iodide and a cell migration assay transwell were used to analyze cell activity western blot analysis and quantitative reversetranscription polymerase chain reaction were performed to examine functionrelated mrna and protein levels treatment with polydatin suppressed cell growth and migration in both cell lines moreover polydatin induced cell apoptosis in both parental and paclitaxelresistant cells and cellcycle arrest in the s phase furthermore it altered the expression of various proteins associated with cell growth ki67 p21 cyclin a cyclin e and cyclindependent kinase 2 migration matrix metalloproteinase2 mmp2 mmp9 and tissue inhibitor of metalloproteinase1 apoptosis polyadpribose polymerase 1 and caspase 3 and drug resistance pglycoprotein 1 lung resistancerelated protein 1 growth arrest and dna damage45 glutathione stransferase and heat shock protein 27 in paclitaxelresistant osteosarcoma cells cells transfected with myrakt caused obvious upregulation and activation of akt which were significantly attenuated via polydatin treatment in conclusion polydatin may enhance the chemosensitivity of osteosarcoma cells to paclitaxel