Reversion of Multidrug Resistance in a Chemoresistant Human Breast Cancer Cell Line by β-Elemene
Publisher:
Karger
E-ISSN:
1423-0313|89|5-6|303-312
ISSN:
0031-7012
Source:
Pharmacology,
Vol.89,
Iss.5-6, 2012-05,
pp. : 303-312
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Abstract
Background: 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 β-elemene on MDR in human breast carcinoma MCF-7 and doxorubicin-resistant MCF-7 cells. Methods: MTT cytotoxicity assays, flow cytometry, and Western blot analysis were performed to investigate the antiproliferative effects of the combination of anticancer drugs with β-elemene, to study the reversal of drug resistance, and to examine the inhibitory effects on protein expression. Results: The results showed that β-elemene (30 µmol/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 β-elemene in reversing P-glycoprotein (P-gp)-mediated MDR demonstrated that β-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 β-elemene could inhibit the expression of P-gp, while it had little effect on the expression of MRP1 protein. In addition, β-elemene had little inhibitory effect on the intracellular GSH levels and GST activities in MCF-7/DOX cells. Conclusions: β-Elemene might represent a promising agent for overcoming MDR in cancer therapy.