Objective: To investigate the mechanism of the reverse effect of quercetin on multidrug resistance (MDR) of human hepalocellular carcinoma (HCC) in the course of genetic transcription. Msthods: Human hepatocellular carcinoma 5-FU resistant cell line Bel-FU was cultured in vitro. The cytotoxicity and dose-dependent reverse effect of quercetin were detected by MTT assay. The gene expression of mdrl, multidrug resistance associated protein (MRP), glutathione-S -transferase-Π (GST-Π), topoisomerase II alpha (Topo Ⅱ α), H-ras and F-glycoprotein (P-gp) were detected by real-time quantitative PCR and western-blot. Results: The 10% inhibitory concentration (IC10) and IC50 of quercetin were 58.2 (μmol/ L and 193.9 fi,mol/L for Bel-FU cells respectively. Quercetin (16.5, 33.0 and 49.5 |j,mol/L) reversed MDR for Bel-FU was 1.14, 1.68 and 2.38 folds respectively. Quercetin down-regulated the gene expression of mdrl, MRP, GST-ir and H-ras (P < 0.05), which were 0.38, 0.27, 0.36 and 0.42 folds respectively, but no effect on Topo II a (P < 0.05). P-gp expression was down-regulated in Bel-FU cells treated with Quercetin (P < 0.05). Conclusion: Quercetin can down-regulate the expression of related gene in resistant cell line and reverse the MDR of human HCC cells.%目的:在基因转录水平上探讨槲皮素逆转人肝癌多药耐药(MDR)的作用机制.方法:采用体外培养人肝癌耐5-氟尿嘧啶细胞Bel-FU,MTT法测定槲皮素的体外细胞毒性及浓度依赖的逆转耐药作用.实时定量PCR以及Western blot检测槲皮素作用后细胞中基因mdr1、多药耐药相关蛋白(MRP)、谷胱甘肽-S-转移酶-π(GST-π)、拓扑异构酶Ⅱα(TopoⅡα)、H-ras和p-糖蛋白(P-gp)的表达变化.结果:槲皮素对Bel-FU细胞的IC10和IC50分别为58.2、193.9μmol/L.16.5、33.0、49.5 μmol/L的槲皮素对Bel-FU的逆转耐药倍数分别为1.14、1.68、2.38倍;槲皮素可下调耐药细胞中基因mdrl、MRP、GST-π、H-ras表达(P＜0.05),下调倍数分别为0.38、0.27、0.36、0.42,而对TopoⅡα无影响(P＞0.05).槲皮素可下调P-gp蛋白在耐药细胞中的表达量(P＜0.05).结论:槲皮素可下调耐药细胞中耐药相关基因的表达量,从而逆转人肝癌细胞的多药耐药性.
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