Esomeprazole overcomes paclitaxel‐resistance and enhances anticancer effects of paclitaxel by inducing autophagy in A549/Taxol cells

Abstract Non‐small‐cell lung cancer (NSCLC) is one of the most common malignancies, and the occurrence of drug‐resistance severely limits the efficacy of anticancer drugs in the treatment of NSCLC. Identification of new agents to reverse drug‐resistance in NSCLC treatment is of great importance and urgency both clinically and scientifically. In the present study, we found that A549/Taxol cells displayed a high level of resistance to paclitaxel with the resistance index up to 231. Importantly, esomeprazole could potentiate the antiproliferative effect of paclitaxel in A549/Taxol cells, but not in A549 cells. Further exploration on the underlying mechanisms revealed that esomeprazole decreased the intracellular pH via inhibiting V‐ATPase expression in A549/Taxol cells. Meanwhile, esomeprazole pretreatment significantly promoted paclitaxel‐induced polymerization of tubulin and enhanced the proportion of G2/M‐arrested cells in A549/Taxol cells. Unfortunately, esomeprazole could only result in a slight decrease in the expression of P‐gp in A549/Taxol cells. Interestingly, esomeprazole significantly increased paclitaxel‐induced apoptosis, which was impeded by the autophagy inhibitor 3‐MA in A549/Taxol cells. Taken together, our data suggest that esomeprazole is a promising chemosensitizer against paclitaxel‐resistant NSCLC by inducing autophagy. Our study also offers a new strategy to solve the paclitaxel‐resistance problem during NSCLC treatment.