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

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.