Study Of The Proliferative And Invasive Migration Effects Of Epothilone B (Patupilone) On Human Osteosarcoma Cells

Background and purpose:Osteosarcoma is the most common primary malignant bone tumor in children and adolescents.More than half of patients develop pulmonary metastases at various stages of the disease course,and its high propensity to metastasize is a major cause of treatment failure and poor prognosis.Although the research of osteosarcoma has greatly evolved over the past decades,the treatment strategies for metastatic progression and recurrence remain scarce,and the prognosis of patients with metastases and recurrences remains unsatisfactory.Epothilone B has been shown to exert anti-tumor effects in a variety of cancers and to be effective against certain paclitaxel-resistant tumor cells.In this study,Epothilone B was found to have inhibitory effects on two human osteosarcoma cell lines,MG63 and 143 B,inhibiting the growth and progression of OS cells in vivo and in vitro and inducing increased apoptosis in osteosarcoma cells.However,the molecular mechanism of the anti-tumor effect of Epothilone B on osteosarcoma is not clear.Therefore,we need to investigate the mechanism related to the inhibitory effect of Epothilone B on osteosarcoma cells in order to develop new therapeutic approaches targeting metastasis and provide a new basis and direction for the clinical treatment of osteosarcoma.Method:We found that Epothilone B has anti-tumor effects in a variety of cancers by reading a lot of literature.We set different concentrations of Epothilone B to treat osteosarcoma cell lines,and examined the effects of different drug concentrations of Epothilone B on proliferation,migration,invasion,apoptosis and subcutaneous tumorigenesis of osteosarcoma cell lines in vivo by CCK-8 assay,clone formation assay,wound healing assay,Transwell assay,flow cytometry analysis and constructed mouse model assay,and western blotting assay to verify the effects of this drug on the expression of osteosarcoma cell-related protein.Results:In this study,we found that Epothilone B inhibited the survival,invasion,migration ability and promoted apoptosis of osteosarcoma cell lines 143 B and MG63 in vitro,and Epothilone B also inhibited the growth of osteosarcoma transplants in vivo.Epothilone B was able to partially block the activation of PI3K/Akt/m TOR signaling pathway.Conclusion:The osteosarcoma cell lines MG63 and 143 B are sensitive to Epothilone B in an in vitro.In vitro,Epothilone B had anti-proliferative,inhibited invasion and migration,and promoted apoptosis of these two osteosarcoma cells at certain effective concentrations.In vivo,Epothilone B also inhibited the growth of transplanted tumors in nude mice.Moreover,its anti-tumor effect may be mediated by blocking the activation of PI3K/Akt/m TOR signaling pathway.