Combination treatment of gemcitabine and sorafenib exerts a synergistic inhibitory effect on non-small cell lung cancer in vitro and in vivo via the epithelial-to-mesenchymal transition process.

Abstract

Standard chemotherapy is commonly used in clinical practice for the treatment of non-small cell lung cancer (NSCLC). However, its therapeutic efficacy remains low. Combination therapy for cancer treatment has attracted attention in recent years. The present study aimed to investigate the antitumor effect of the combination treatment with gemcitabine and sorafenib on NSCLC in vitro and in vivo, and to determine its underlying molecular mechanisms. The anti-NSCLC effects of combination therapy were analyzed by flow cytometry analysis, MTT, western blotting, reverse transcription-quantitative PCR, wound healing and Transwell invasion assays. A549 cells subjected to combination treatment with gemcitabine and sorafenib demonstrated a more irregular cellular morphology and lower cell viability compared with the monotherapy groups. Combination of gemcitabine and sorafenib significantly induced cell cycle arrest and apoptosis in A549 cells. Additionally, combination therapy was demonstrated to restrain the migration and invasion of tumor cells by suppressing epithelial-to-mesenchymal transition (EMT) of A549 cells. In vivo analyses confirmed that co-treatment with gemcitabine and sorafenib decreased NSCLC tumor growth and tumor weight in nude mice. Taken together, the results of the present study suggested that combination treatment with gemcitabine and sorafenib exerted a synergistic inhibitory effect on NSCLC in vitro and in vivo via the EMT process.