title: Trametenolic acid B reverses multidrug resistance in breast cancer cells through regulating the expression level of P-glycoprotein.
abstract: Trametenolic acid B (TAB) is the main active composition of Trametes lactinea (Berk.) Pat which possesses antitumor activities. There was no report its antitumor effect through regulating P-glycoprotein (P-gp) so far, due toP-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 rhodamine 123 (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.
authors.affiliation: 1Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang, Hubei 443002, China.
authors.forename: Qiaoyin
authors.initials: Q
authors.lastname: Zhang
authors.forename: Junzhi
authors.initials: J
authors.lastname: Wang
authors.forename: Haibo
authors.initials: H
authors.lastname: He
authors.forename: Hongbing
authors.initials: H
authors.lastname: Liu
authors.forename: Ximing
authors.initials: X
authors.lastname: Yan
authors.forename: Kun
authors.initials: K
authors.lastname: Zou
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D017239:Paclitaxel / Q000494:pharmacology; D055454:Trametes / Q000737:chemistry; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014315:Triterpenes; C586576:trametenolic acid B; D017239:Paclitaxel