Autophagy inhibition impairs the epithelial-mesenchymal transition and enhances cisplatin sensitivity in nasopharyngeal carcinoma.

Abstract

Drug resistance restricts the efficacy of cisplatin in the treatment of nasopharyngeal carcinoma (NPC). Increasing evidence indicates that autophagy and the epithelial-mesenchymal transition (EMT) participate in cancer progression and drug sensitivity. The aim of the present study was to investigate the function of autophagy and EMT in cisplatin treatment, and to reveal the underlying impact of autophagy on the EMT process in NPC. Transmission electron microscopy assays and western blot analyses confirmed that cisplatin activates autophagy in NPC cells. Alterations in cell morphology and biomolecular markers confirmed that cisplatin induces the EMT phenotype in NPC cells. Cell viability assays showed that the combination of the autophagy inhibitor chloroquine (CQ) increased the cytotoxicity of cisplatin in NPC cells and that the EMT inducer transforming growth factor β1 promoted the resistance to cisplatin in NPC cells. Moreover, autophagy inhibition by CQ and microtubule-associated protein 1 light chain 3B-knockdown reversed the EMT phenotype in NPC cells. In conclusion, autophagy and the EMT process promote cisplatin resistance in NPC cells, while the inhibition of autophagy impairs the EMT process.