大黄酸对耐顺铂A549/cDDP细胞株的耐药逆转作用及机制研究  

Study on the efficiency and mechanisms of rhein on revering cisplatin resistance of human lung cancer cell line A549/cDDP

作　　者：陈奕芝[1] 刘锦新[1] 谭烁[1] 李铁锋工[1] 廖镜云[1] 钱有为[2] 

机构地区：[1]深圳市龙岗中心医院,广东深圳518116 [2]广东药学院药物制剂系,广东广州510006

出　　处：《热带医学杂志》2013年第10期1218-1220,1230,共4页Journal of Tropical Medicine

基　　金：深圳市龙岗区医疗卫生科技计划项目(YLL2010066)

摘　　要：目的观察大黄酸对耐顺铂(cDDP)A549/cDDP细胞的耐药逆转作用并探讨其可能的作用机制。方法用不同浓度的大黄酸与耐药细胞A549/cDDP共同培养,通过MTT法检测细胞增殖抑制率并确定大黄酸逆转耐药最佳浓度;将对数生长期的细胞随机分成2组,对照组分别加入不同浓度的cDDP,实验组在对照组基础上加入2μg/ml的大黄酸,同时设空白对照组,采用MTT法测算细胞增殖抑制率,计算两组细胞cDDP的半数抑制浓度(IC50)及大黄酸的逆转耐药倍数;将对数生长期的细胞分为2组,对照组加入2μg/ml cDDP,实验组在对照组的基础上加入2μg/ml的大黄酸,同时设空白对照组,流式细胞仪检测各组细胞P蛋白(P-gp)及多药耐药相关蛋白-1(MRP-1)的表达。结果随着大黄酸浓度的增加,其细胞增殖抑制率不断增加(P<0.05),大黄酸逆转耐药的最佳浓度为2μg/ml;对照组IC50为31.642μg/ml,实验组IC50为21.412μg/ml,大黄酸的逆转耐药倍数为1.48倍;大黄酸能下调A549/cDDP细胞P-gp及MRP的表达。结论大黄酸可逆转耐cDDP的A549/cDDP细胞株的耐药性,其作用机制可能与下调P-gp及MRP-1蛋白表达有关。Objective To explore the effect and mechanism of rhein on revering cisplatin （cDDP） resistance of human lung cancer cell line A549/cDDP. Methods A549/cDDP cells were cultured with different concentrations of rhein. MTr assay was used to detect the cell proliferation inhibition rate, and to determine the optimal concentration of rhein for the reversing drug resistance. A549/cDDP cells were divided into two groups. Cells. in control group were cultured with different concentrations of cDDP, and cells in experimental group were given 2 μg/ml rhein on the basis of the control group.MTr assay was used to detect the cell proliferation inhibition rate, and ICso and reversing multiple were calculated. A549/cDDP cells were divided into blank control group,positive control group（2 μg/ml cDDP） and experimental group （2 μg/ml cDDP＋2 μg/ml rhein）, after 24 hours, P-glycoprotein（P-gp） and muhi-drug resistance protein-1 （MRP-1） were analyzed by flow cytometry. Results Rhein could inhibit cell proliferation in dose dependent manner, with an optimal concentration of rhein reversing drug resistance of 2 μg/ml. IC50 of cDDP in control group was 31.642 μg/ml, and 21.412 μg/ml in experimental group, and the drug-resistant muhiple of RH was 1.48. The expression of P-gp and MRP-1 were down-regulated by RH. Conclusions Rhein could reverse cDDP resistance of A549/cDDP. The mechanism may be correlated to the down-regulating expression of P-gp and MRP-1.

关 键 词：大黄酸 A549 cDDP细胞 顺铂 P蛋白 多药耐药相关蛋白-1 

分 类 号：R73-36[医药卫生—肿瘤]