Tragomycin A Enhances Chemosensitivity to Cisplatin in Ovarian Cancer Cell Lines by Down-regulating STAT3 / 华中科技大学学报(医学版)

ABSTRACT

Objective@#Our study aimed to investigate the effect of histone deacetylase inhibitor trichostatin A（TSA）on the cisplatin（CDDP） resistance of ovarian cancer cell lines and its molecular mechanism.@*Methods@#Cisplatin-resistant ovarian cancer cell line C13* and its parental line OV2008 were incubated with TSA（200 nmol/L） or/and CDDP（20 μmol/L），the inhibitory rate of tumor cells was determined by MTT assay. Flow cytometry and Western blotting were used to detect apoptosis of tumor cells. Western blotting was also used to detect STAT3 expression in C13* and OV2008 cells. After down-regulation of STAT3 by transfection of STAT3 siRNA in C13* cells，cisplatin-induced apoptosis was evaluated by flow cytometry.@*Results@#MTT assay showed that the proliferation inhibitory rates of the combination group after 48 or 72 h treatment were significantly higher than those of TSA and CDDP groups. The level of STAT3 protein was much higher in C13* cells than in OV2008 cells. Flow cytometry and Western blotting showed that TSA combined with CDDP significantly enhanced the apoptotic rate of C13* cells. STAT3 expression level was significantly higher in C13* cells than in OV2008. Downregulation of STAT3 can significantly improve CDDP-induced apoptosis of C13* cells. @*Conclusion@#Down-regulation of STAT3 by TSA endows cisplatin-resistant cells C13* with increased sensitivity to cisplatin.