Trametenolic Acid B Reverses Multidrug Resistance in Breast Cancer Cells Through Regulating the Expression Level of P-Glycoprotein

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Abstract

Trametenolic acid B (TAB) is the main active composition of Trametes lactinea (Berk.) Pat which possesses anti-tumor activities. There was no report its antitumor effect through regulating P-glycoprotein (P-gp) so far, due to P-gp over expression is one of the most important mechanisms contributing to the multiple drug resistance phenotype. The present aim was to investigate the effects of TAB on P-gp in multidrug-resistant cells; Paclitaxel-resistant cell line MDA-MB-231/Taxol was established by stepwise exposure for 10 months. MDA-MB-231 cells and MDA-MB-231/Taxol cells were treated with TAB, and their growth was evaluated using MTT assays. Paclitaxel accumulation in the cells was analyzed by high performance liquid chromatogram (HPLC). The activity of P-gp was detected by intracellular accumulation of rhodamine123 (Rho123), and the protein expression of P-gp was evaluated using western blot. Results indicated that the IC50 of MDA-MB-231/Taxol to paclitaxel (Taxol) was 33 times higher than that of nature MDA-MB-231. TAB increased the intracellular concentration of Taxol and inhibited the activity of P-gp and suppressed the expression of P-gp in MDA-MB-231/Taxol cells. Our present results showed that TAB could reverse Taxol resistance in MDA-MB-231/Taxol cells, mainly inhibiting the activity of P-gp and down-regulating the expression level of P-gp, and then enhancing the accumulation of chemotherapy agents. © 2013 The Authors Phytotherapy Research Published by John Wiley & Sons Ltd.

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