Elemene Increases Autophagic Apoptosis and Drug Sensitivity in Human Cisplatin (DDP)-Resistant Lung Cancer Cell Line SPC-A-1/DDP By Inducing Beclin-1 Expression

Abstract

Drug resistance is the major obstacle for the successful therapy of lung adenocarcinoma. It was suggested that ß-elemene, a major isoform of elemene, could reverse the drug resistance in lung cancer cells. However, the underlying mechanisms remains poorly known. Here, we aimed to investigate whether elemene is involved in the cisplatin (DDP)-resistance of lung adenocarcinoma cells and further explore the underlying mechanism. The results showed that human lung adenocarcinoma cell line SPC-A-1 and its DDP-resistant strain SPC-A-1/DDP had a similar sensitivity to elemene treatment. Low dose elemene increased the sensitivity of SPC-A-1/DDP cells to DDP, accompanied by a dramatically decrease in expression of multidrug-resistance proteins and cell proliferation, and an increase in cell autophagy and autophagic apoptosis. We found that the expression of Beclin-1, the key regulator of autophagy, was induced by elemene treatment in a dose-dependent manner. Furthermore, we found that Beclin-1 overexpression had a similar effect with elemene treatment on autophagy and autophagic apoptosis in SPC-A-1/DDP cells. In contrast, Beclin-1 knockdown could significantly rescue elemene-induced autophagic apoptosis and counteract elemene-induced sensitivity in SPC-A-1/DDP cells. Our findings demonstrate that elemene can reverses the drug resistance of SPC-A-1/DDP cells via promotion of Beclin-1-induced autophagy.