槲皮素对阿霉素诱导HL-60细胞MDR1基因表达的影响  

Effect of Quercetin on Doxorubicin-induced Expression of MDR1Gene in HL-60 Cells

作　　者：何海兰[1] 季丽娟[1] 李琦智[2] 张熔[1] 黄建鸣[2] 李戈[1] 

机构地区：[1]四川省医学科学院.四川省人民医院儿科,四川成都610072 [2]四川省肿瘤医院肿瘤研究所,四川成都610041

出　　处：《中国实验血液学杂志》2015年第1期70-76,共7页Journal of Experimental Hematology

基　　金：四川省科技厅科研基金(05JY029-039)

摘　　要：目的:本研究探讨槲皮素对阿霉素诱导人急性髓系白血病细胞株(HL-60细胞)多药耐药基因1(MDR1)mRNA和环氧化酶2(COX2)mRNA共表达的影响。方法:采用RT-PCR检测HL-60细胞MDR1和COX2 mRNA的表达;酶联免疫吸附法测定HL-60细胞前列环素E2(PGE2)的释放;MTT法检测阿霉素的细胞毒作用。结果:阿霉素可诱导HL-60细胞MDR1和COX2 mRNA过表达;槲皮素可下调阿霉素诱导的COX2依赖的MDR1 mRNA过表达,显著降低阿霉素诱导的PGE2释放,增加阿霉素的细胞毒作用。结论:阿霉素诱导COX2和MDR1的共表达存在相关性;阿霉素诱导的MDR1上调可能依赖于COX2转录后的激活,槲皮素对COX2表达的调节作用不仅增加白血病细胞对阿霉素的敏感性,而且可以预防白血病化疗中多药耐药的产生。Objective： Leukemia cells can acquire a multidrug resistant （MDR） phenotype in response to a wide variety of chemotherapeutic agents including doxorubicin （Dox）. In addition to the constitutive expression in the leukemia prior to chemotherapy, a complex phenotype of pleiotropic resistance is presented in the residual or recurrent leukemia. Recent studies showed Dox-induced coexpression of COX2 and MDR1 genes in human leukaemia cells, and whether Dox-induced MDR1 up-regulation in acute leukaemia cells is dependent on COX2-transcriptional activity and thus might be overcome or prevented with COX2-promotor inhibitor quercetin interfering with COX2 expression and activity. This study was purposed to investigate the impacts of quercetin on Dox-induced mRNA expression of MDR1 and COX2 genes in HL-60 leukemia cells. Methods： The MDR1 and COX2 mRNA expression in HL-60 cells was detected by RT-PCR; the prostaglandin E2 （ PGE2 ） release was measured by ELISA; the cytotoxicity of Dox was determined by MTT test. Results： The incubation of HL-60 cells with Dox not only up-regulated MDR1 mRNA, but also COX2 mRNA expression, and after co-incubation with quercetin or celecoxib, Dox-induced overexpression of MDR1 and COX2 mRNA were reduced by quercetin, not by celecoxib, whereas PGE2 release was significantly decreased with subsequent enhancement of Dox cytotoxic efficacy by both of them. Conclusions ： Dox-induced MDR1 up-regulation may be dependent on COX2- transcriptional activity, not PGE2, suggesting that the existence of causal link between COX2 and MDR1 expression induced by Dox, and modulation of COX2 transcriptional expression by quercetin would not only sensitize leukemia cells to Dox, but also prevent the acquisition of MDR during chemotherapy.

关 键 词：多药耐药基因1 环氧化酶2 塞来考昔 槲皮素 阿霉素 HL-60白血病细胞株 

分 类 号：R733.71[医药卫生—肿瘤]