Preliminary evaluation of the potential role of β‑elemene in reversing erlotinib‑resistant human NSCLC A549/ER cells

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.