Pin1 modulates chemo-resistance by up-regulating FoxM1 and the involvements of Wnt/β-catenin signaling pathway in cervical cancer

The prolyl isomerase Pin1, which is frequently highly expressed in many different cancers, can directly regulate cell proliferation and the cell cycle. However, the role of Pin1 in chemo-resistance remains to be elucidated in cervical cancer. The purpose of the present study was to investigate the role of Pin1 in the chemo-resistance of cervical cancer. The cisplatin resistance was assessed using the MTT assay. Pin1, FoxM1, beta-catenin, Cyclin D1, and c-myc expression levels were detected by RT-qPCR or Western blot. The results showed that Pin1 expression displayed a similar expression pattern with the resistance to cisplatin in five cervical cell lines. Knockdown of Pin1 significantly increased the sensitivity to cisplatin in HeLa cells, while Pin1 overexpression decreased the sensitivity to cisplatin in Me180 cells. Knockdown of Pin1 significantly down-regulated FoxM1 expression in HeLa cells, while Pin1 overexpression showed a contrary effect in Me180 cells. Besides, overexpression of Pin1 markedly increased the protein expression of beta-catenin and its target genes cyclin D1 and c-myc. FoxM1 siRNA remarkably reversed the promotory effect of pcDNA-Pin1(+) on beta-catenin and its target genes cyclin D1 and c-myc in Me180 cells. Furthermore, we also found that FoxM1 siRNA and IWP-2 markedly decreased cell viability, and IWP-2 decreased cell viability to the maximum extent in the Me180 cells co-transfected with pcDNA-Pin1(+) and FoxM1 siRNA. Taken together, these data suggest that Pin1 contributes to cisplatin resistance, partly by up-regulating FoxM1 and Wnt/beta-catenin signaling pathway involved in cervical cancer.