Olanzapine Ehhances The Sensitivity Of Temozolomide-Resistant Glioma Cells

Objective:The aim of this study is to investigate whether apoptosis will be increased in temozolomide-resistant glioma cells employing the combination therapy of TMZ and OLZ, and researching the mechanism of it, using glioma cell lines T98^ U87 and LN229 cells as models.Methods:Cell viability was tested by using the method of MTT and Colony formation; Hochest 33258 and Annexin V/PI flow cytometry werer carried out to investigate the toxic effects of temozolomide and olanzapine on model glioma cells. Western blotting was used to detect MGMT, apoptosis related protein Bcl-2 and autophagy related proteins LC-3, p62 expression level.Results:MTT assay and colony formation assay shows that temozolomide and olanzapine are both cytotoxic to glioma cells by detecting cell viability, and the toxic effect is time and dose-dependent; Annexin V/PI double staining flow cytometry, Hoechst staining and western blot which used to testing Bcl-2 show the level of apoptosis and proved that the combination therapy of olanzapine and temozolomide produced a synergistic effect that enhances the apoptosis to glioma cells; Western blot approved that the resistance of temozolomide-resistant cell was regulated by MGMT gene, and the expression of MGMT reduced after combined with olanzapine. Besides,western blot can also detect the expression of autophagy-related protein.Conclusion:Olanzapine combines temozolomide inhibiting the growth of glioma cells,especially in TMZ-resistant glioma, accompanied by the induction of autophagy and apoptosis.