艾迪注射液对人肝癌细胞株多药耐药性的逆转作用  

A Research on Reversal Effect of Aidi Injection to Multidrug-resistant Human Hepatocellular Carcinoma Cell Line

作　　者：喻贡金 李红霞[1,2] 喻超[1,2] 刘兴贵[1,2] YU Gongjin LI Hongxia YU Chao LIU Xinggui(Department of Liver and Gall Surgery, the Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China Key Laboratory of Hepatobiliary and Pancreatic Surgery, Guizhou Medical University, Guiyang 550004, Guizhou, China)

机构地区：[1]贵州医科大学附院肝胆外科,贵州贵阳55004 [2]贵州医科大学肝胆胰脾重点实验室,贵州贵阳550004

出　　处：《贵州医科大学学报》2017年第7期759-762,771,共5页Journal of Guizhou Medical University

基　　金：国家自然科学基金项目(81560477);贵州省卫生计生委科学技术基金(gzwjkj 2014-2-112);贵州省科学技术基金[黔科合J字(2015)2013号];贵州省"肝胆胰脾疾病诊治"导师工作室[黔教研合GZS(2016)09];贵州省肝胆外科临床医学研究中心[黔科合平台人才(2017)5404]

摘　　要：目的:探讨艾迪注射液对人肝癌细胞株Bel-7402/5-FU多药耐药性(MDR)的逆转作用及可能机制。方法:采用5-氟尿嘧啶(5-FU)药物浓度梯度递增法建立人肝癌MDR细胞株Bel-7402/5-FU,采用cck-8法检测Bel-7402及Bel-7402/5-FU对5-FU、阿霉素(ADM)、丝裂霉素(MMC)、甲氨蝶呤(MTX)、环玲酰胺(CTX)及顺铂(CDDP)6种化疗药物的敏感性、并计算半数致死浓度(IC50)及6种化疗药物对Bel-7402/5-FU细胞的IC50及耐药指数(RI),同时观察不同浓度艾迪注射液对Bel-7402/5-FU细胞的抑制率,Western blot法检测经过IC50艾迪注射液处理的Bel-7402/5-FU细胞中多药耐药相关蛋白1(MRP1)、P-糖蛋白(P-gp)、程序化死亡因子5蛋白(PDCD5)的表达水平。结果:6种化疗药物对Bel-7402/5-FU细胞株的IC50较Bel-7402细胞株明显升高,与Bel-7402细胞相比,Bel-7402/5-FU细胞株中MRP1、P-gp表达明显升高,PDCD5表达明显降低(P<0.05);经IC50艾迪注射液处理后的Bel-7402/5-FU细胞中升高的MRP1、P-gp表达和PDCD5降低得到抑制(P<0.05)。结论:艾迪注射液具有逆转肝癌细胞MDR的作用,其机制可能与下调多药耐药相关蛋白MRP1、P-gp表达,上调凋亡相关蛋白PDCD5的表达有关。Objective： To explore the reversal effect of Aidi injection to human hepatoma cell line, Bel-7402/5-FU, a multidrug-resistant strain, and the possible mechanism. Methods： The multidrug- resistant human hepatocellular carcinoma Bel-7402/5-FU was established by increasing concentrations of fluorouracil （5-FU）. The sensitivities of BEL-7402 and Bel-7402/5-fu to six kinds of chemotherapy drugs （5-FU, ADM, MMC, MTX, CTX, and CDDP）, and sensitivity of Bel-7402/5-FU to Aidi injection were tested with CCK-8 method. Half lethal concentrations （ICs0） of the 6 drugs to Bel-7402/ 5-FU, and resistence index （RI） of Bel-7402/5-FU to these drugs were calculated. The inhibitory rates of different consentrations of Aidi injection to Bel-7402/5-FU were observed. Expression levels of resistance related protein 1 （MRP1）, P-glucose protein （P-gp）, and programmed cell death 5 （PDCD5） in Bel-7402/5-FU cells treated by Aidi injection of ICs0 concentration were detected with Western blot. Results： ICs0s of the 6 drugs to Bel-7402/5-FU were significantly higher than those to Bel-7402; In Bel-7402/5-FU cells, the protein expression levels of MRP1 and P-gp were obviously higher and the expression level of PDCD5 protein was lower than those in Be17402 cells （ P 〈 0.05 ） ; The expression of MRP1 and P-gp proteins was down-regulated after Aidi injection treatment, while the PDCD5 protein was significantly incrased （ P 〈 0.05 ）. Conclusion： The Aidi injection can reverse multi-drug resistance of the Bel-7402/5-FU cell line. The mechanisms might associate with down-regu- lation of MRP1 and P-gp, and up-regulation of PDCD5.

关 键 词：多药耐药 半数致死浓度 耐药指数 交叉耐药 艾迪注射液 

分 类 号：R73-36[医药卫生—肿瘤] R735.7[医药卫生—临床医学]