Reversion of multidrug resistance in a chemoresistant human breast cancer cell line by β-elemene

Pharmacology
Hong-Bin XuLu-Zhong Xu

Abstract

Multidrug resistance (MDR) presents a problem in cancer chemotherapy, and developing new agents to overcome MDR is important. This study intends to investigate the reversal effect of -elemene on MDR in human breast carcinoma MCF-7 and doxorubicin-resistant MCF-7 cells. MTT cytotoxicity assays, flow cytometry, and Western blot analysis were performed to investigate the antiproliferative effects of the combination of anticancer drugs with -elemene, to study the reversal of drug resistance, and to examine the inhibitory effects on protein expression. The results showed that -elemene (30 μ mol/l) had a strong potency to increase the cytotoxicity of doxorubicin to MCF-7/DOX cells, with a reversal fold of 6.38. In addition, the mechanisms of -elemene in reversing P-glycoprotein (Pgp)-mediated MDR demonstrated that -elemene significantly increases the intracellular accumulations of doxorubicin and Rh123 via inhibition of the P-gp transport function in MCF-7/DOX cells. Flow cytometry and Western blot analyses revealed that -elemene could inhibit the expression of P-gp, while it had little effect on the expression of MRP1 protein. In addition, -elemene had little inhibitory effect on the intracellular GSH levels and GST activities in MC...Continue Reading

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