艾迪注射液对人肝癌细胞株多药耐药性的逆转作用

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(MRPl)、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 multidrugresistant 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 IC50concentration were detected with Western blot.Results:IC50s 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-regulation of MRP1 and P-gp,and up-regulation of PDCD5.