Department of Histology and Embryology, Medical University, T. Chalubinski Street 6a, 50-368 Wroclaw, Poland.
Molecules. 2010 Feb 9;15(2):857-70. doi: 10.3390/molecules15020857.
P-glycoprotein (P-gp) is one of the ABC transporters responsible for the resistance of several tumours to successful chemotherapy. Numerous agents are capable of interfering with the P-gp-mediated export of drugs but unfortunately most of them produce serious side effects. Some plant polyphenols, including the flavonol quercetin (Q), manifest anti-neoplastic activity mainly due to their influence on cell cycle control and apoptosis. Reports are also available which show that Q may intensify action of cytostatic drugs and suppress the multidrug resistance (MDR) phenomenon. The study aimed at determination if Q sensitizes cells resistant to daunorubicin (DB) through its effect on P-gp expression and action. The experiments were conducted on two cell lines of human pancreatic carcinoma, resistant to DB EPP85-181RDB and sensitive EPP85-181P as a comparison. Cells of both lines were exposed to selected concentrations of Q and DB, and then membranous expression of P-gp and its transport function were examined. The influence on expression of gene for P-gp (ABCB1) was also investigated. Results of the studies confirmed that Q affects expression and function of P-gp in a concentration-dependent manner. Moreover it decreased expression of ABCB1. Thus, Q may be considered as a potential modulator of P-gp.
P-糖蛋白(P-gp)是一种 ABC 转运蛋白,负责多种肿瘤对成功化疗的耐药性。许多药物能够干扰 P-gp 介导的药物外排,但不幸的是,大多数药物会产生严重的副作用。一些植物多酚,包括类黄酮槲皮素(Q),主要通过影响细胞周期控制和细胞凋亡来表现出抗肿瘤活性。也有报道表明,Q 可能增强细胞毒药物的作用,并抑制多药耐药(MDR)现象。本研究旨在确定 Q 是否通过影响 P-gp 的表达和作用来使对柔红霉素(DB)耐药的细胞敏感化。实验在两种人胰腺癌细胞系上进行,一种是对 DB 耐药的 EPP85-181RDB 细胞系,另一种是作为对照的敏感 EPP85-181P 细胞系。用选定浓度的 Q 和 DB 处理两种细胞系的细胞,然后检测 P-gp 的膜表达及其转运功能。还研究了对 P-gp(ABCB1)基因表达的影响。研究结果证实,Q 以浓度依赖的方式影响 P-gp 的表达和功能。此外,它还降低了 ABCB1 的表达。因此,Q 可以被认为是 P-gp 的潜在调节剂。