Pantoprazole promotes the sensitivity of cervical cancer cells to cisplatin by inhibiting cisplatin-induced autophagy.

Abstract

This study aimed to explore the role of pantoprazole (PPZ) in affecting the sensitivity of cervical cancer (CC) cells to cisplatin. HeLa and CaSki cells were exposed to cisplatin and/or PPZ treatment. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation, flow cytometry, wound healing, and transwell assays were performed to detect cell viability, proliferation, apoptosis, migration, and invasion of CC cells, respectively. Then, expressions of Beclin-1, LC3, and p62 were measured by western blot. Rapamycin (Rapa), acting as an autophagy activator, was applied to confirm the effect of autophagy on the sensitivity of CC cells to cisplatin. Cisplatin treatment suppressed cell viability and proliferation and accelerated apoptosis of CC cells. Combination of cisplatin and PPZ or PPZ alone significantly inhibited cell viability, proliferation, migration, and invasion, and increased cell apoptosis of CC cells. Cisplatin enhanced expression levels of Beclin1 and LC3II/I, and reduced p62 expression. Combination of cisplatin and PPZ significantly decreased the expression levels of Beclin1 and LC3II/I, but increased p62 expression. The autophagy activator, Rapa, eliminated the inhibitory effects of the combination of cisplatin and PPZ on autophagy, and enhanced cell viability, but inhibited apoptosis of CC cells. PPZ promotes the sensitivity of CC cells to cisplatin by inhibiting cisplatin-induced cell autophagy.