三萜烯酸 B 通过调节 P-糖蛋白的表达水平逆转乳腺癌细胞的多药耐药性。
Trametenolic acid B reverses multidrug resistance in breast cancer cells through regulating the expression level of P-glycoprotein.
机构信息
1Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang, Hubei 443002, China.
出版信息
Phytother Res. 2014 Jul;28(7):1037-44. doi: 10.1002/ptr.5089.
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.
三萜烯酸 B（TAB）是云芝（Trametes lactinea（Berk.）Pat）的主要活性成分，具有抗肿瘤活性。到目前为止，由于 P-糖蛋白（P-gp）过表达是导致多药耐药表型的最重要机制之一，因此没有关于 TAB 通过调节 P-gp 发挥抗肿瘤作用的报道。本研究旨在探讨 TAB 对多药耐药细胞中 P-gp 的影响；采用逐步暴露法，用紫杉醇（Taxol）处理 10 个月，建立紫杉醇耐药细胞系 MDA-MB-231/Taxol。用 TAB 处理 MDA-MB-231 细胞和 MDA-MB-231/Taxol 细胞，用 MTT 法评估细胞生长情况。用高效液相色谱法（HPLC）分析细胞内紫杉醇的积累。用罗丹明 123（Rho123）的细胞内积累检测 P-gp 的活性，并通过 Western blot 评估 P-gp 的蛋白表达。结果表明，MDA-MB-231/Taxol 对紫杉醇（Taxol）的 IC50 是天然 MDA-MB-231 的 33 倍。TAB 增加了 Taxol 在细胞内的浓度，抑制了 P-gp 的活性，并抑制了 MDA-MB-231/Taxol 细胞中 P-gp 的表达。本研究结果表明，TAB 可以逆转 MDA-MB-231/Taxol 细胞对 Taxol 的耐药性，主要通过抑制 P-gp 的活性和下调 P-gp 的表达水平，从而增强化疗药物的积累。
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