Fig. 7

Proposed model for the mechanism of sequential metformin and cisplatin treatment. Metformin directly phosphorylated YAP1 and inhibited the translocation of YAP1 from the cytoplasm to the nucleus. Low nucleus protein of YAP1 decreased expression of cyclinD1, CDK6, CDK4 and led to G1 phase arrest in TCam-2 and NTERA-2. After withdrawing the metformin for 24 h, most of the cells were synchronized and ready to enter S and G2 phase, which enhanced their chemosensitivity to cisplatin. Therefore, sequential treatment (metformin-cisplatin) could enhance the chemosensitivity of cells and induce apoptosis