Inhibition of STAT3 reverses Taxol-resistance in ovarian cancer by down-regulating G6PD expression in vitro

Abstract

Ovarian cancer is the eminent gynecological malignancy and chemoresistance remains a major reason for poor in ovarian cancer patients. Taxol has been proved as the most effective chemotherapeutic agent against ovarian cancer. However development of Taxol resistance remains a major problem. Here, we report that STAT3, directly activates pentose-phosphate pathway to exert pro-oncogenic effects on Taxol resistance of ovarian cancer. In addition, we found that STAT3, p-STAT3 and glucose-6-phosphate dehydrogenase (G6PD) protein levels are upregulated in Taxol resistant cell lines compared with Taxol sensitive cell lines. Furthermore, inhibition of STAT3 decreased G6PD mRNA expression level and enhanced the sensitivity of Taxol resistant cell to Taxol. Finally, we found that STAT3 directly binds to the G6PD promoter region and promotes the expression of G6PD at transcriptional level. Taken together, our data indicate that activation of STAT3 promotes ovarian cancer cell proliferation, colony formation, and Taxol resistance via augmenting G6PD expression and pentose-phosphate metabolism flux, which provides a potential therapeutic target that may improve prognosis by decreasing G6PD expression and enhancing Taxol-sensitivity.