Abstract
β-elemene (β-ELE) is a natural compound extracted from Curcuma zedoaria Roscoe that has shown promise as a novel anticancer drug to treat malignant tumors. Recent studies have demonstrated that β-ELE can reverse the drug resistance of tumor cells. To the best of our knowledge, there are no reports concerning the reversal of erlotinib resistance by β-ELE in human non-small cell lung cancer (NSCLC) cells. Therefore, the present study investigated the effects of β-ELE on erlotinib-resistant human NSCLC A549/ER cells in vitro and its possible mechanism of action. The sensitivity of A549/ER cells to erlotinib, the cytotoxicity of β-ELE on the growth of A549/ER cells and the effects of β-ELE on the reversal of drug resistance in A549/ER cells were determined by MTT assay. The cell apoptosis rate, cell cycle phase distribution and intracellular rhodamine 123 (Rh123) fluorescence intensity were detected by flow cytometry. The expression level of P-glycoprotein (P-gp) was detected by western blotting. A549/ER cells had a stable drug-resistance to erlotinib. β-ELE inhibited the proliferation of A549/ER cells in a time- and dose-dependent manner, enhanced the sensitivity of A549/ER cells to erlotinib and reversed the drug resistance in A549/ER cells. Treatment with 15 µg/ml β-ELE combined with 10 µmol/l erlotinib caused an increased rate of cell apoptosis and G0/G1 phase arrest. Furthermore, β-ELE reduced the efflux of Rh123 from A549/ER cells, increased the intracellular accumulation of Rh123 and decreased the expression of P-gp. The results of the present study indicated that β-ELE could reverse drug resistance in erlotinib-resistant human NSCLC A549/ER cells in vitro through a mechanism that may involve the decreased expression of P-gp, inhibition of P-gp dependent drug efflux and the increased intracellular concentration of anticancer drugs.