College of Pharmacy, Nankai University, Tianjin 300071, China.
Food Chem. 2013 Feb 15;136(3-4):1117-21. doi: 10.1016/j.foodchem.2012.09.059. Epub 2012 Sep 28.
Overexpression of P-glycoprotein (P-gp) and multidrug resistance-associate protein 1 (MRP1) is a major mechanism leading to multidrug resistance (MDR) of cancer cells. These transporters expel anti-cancer drugs and greatly impair therapeutic efficacy of chemotherapy. A Chinese herbal plant Yanhusuo (Corydalis yanhusuo W.T. Wang, YHS) is frequently used in functional food and traditional Chinese medicine to improve the efficacy of chemotherapy. The objective of this work was to study effects of glaucine, an alkaloid component of YHS, on P-gp and MRP1 in resistant cancer cells. The resistant cancer cell line, MCF-7/ADR and corresponding parental sensitive cells were employed to determine reversal properties of glaucine. Glaucine inhibits P-gp and MRP1-mediated efflux and activates ATPase activities of the transporters, indicating that it is a substrate and inhibits P-gp and MRP1 competitively. Furthermore, glaucine suppresses expression of ABC transporter genes. It reverses the resistance of MCF-7/ADR to adriamycin and mitoxantrone effectively.
多药耐药相关蛋白 1（MRP1）和 P 糖蛋白（P-gp）的过度表达是导致癌细胞多药耐药（MDR）的主要机制。这些转运蛋白会排出抗癌药物，极大地损害化疗的疗效。一种中药植物延胡索（Corydalis yanhusuo W.T. Wang，YHS）常用于功能性食品和中药中，以提高化疗的疗效。本工作的目的是研究延胡索中的一种生物碱成分——格尔碱对耐药癌细胞中 P-gp 和 MRP1 的影响。采用耐药癌细胞系 MCF-7/ADR 及其相应的亲本敏感细胞来确定格尔碱的逆转特性。格尔碱抑制 P-gp 和 MRP1 介导的外排，并激活转运蛋白的 ATP 酶活性，表明它是底物并竞争性抑制 P-gp 和 MRP1。此外，格尔碱抑制 ABC 转运体基因的表达。它能有效逆转 MCF-7/ADR 对阿霉素和米托蒽醌的耐药性。
