TRAIL逆转人胃腺癌SGC7901/ADR细胞多药耐药的机制探讨  

Mechanism of TRAIL reversing multidrug resistance of human gastric adenocarcinoma SGC7901/ADR cells

作　　者：孙海兵[1] 张开光[1] 李琴[1] 刘应玲[1] 陈思[1] 

机构地区：[1]安徽医科大学附属省立医院,合肥230001

出　　处：《山东医药》2017年第13期9-12,共4页Shandong Medical Journal

基　　金：安徽省自然科学基金资助项目(1308085MH167)

摘　　要：目的探讨肿瘤坏死因子相关凋亡诱导配体(TRAIL)对人胃腺癌阿霉素耐药细胞(SGC7901/ADR细胞)多药耐药基因(MDR1)、多药耐药相关蛋白1(MRP1)、抗凋亡基因Bcl-2和促凋亡基因Bax表达的影响,以明确TRAIL逆转胃癌多药耐药的可能机制。方法 MTT法检测SGC7901/ADR细胞和其亲本细胞SGC7901对阿霉素、长春新碱、顺铂的药物敏感性。实时荧光定量PCR法检测SGC7901/ADR细胞和SGC7901细胞MDR1、MRP1、Bcl-2、Bax mRNA表达。不同浓度(10、50、100 ng/m L)TRAIL处理SGC7901/ADR细胞后,使用实时荧光定量PCR法、蛋白印迹法检测各处理细胞和空白对照(未加TRAIL)细胞MDR1、MRP、Bcl-2、Bax mRNA及蛋白的表达。结果药物敏感试验显示,与亲本细胞SGC7901相比,长春新碱、阿霉素、顺铂对SGC7901/ADR细胞的IC50明显提高(P<0.01或<0.05)。SGC7901/ADR细胞中MDR1、MRP1、Bcl-2的mRNA表达量与亲本细胞SGC7901相比上升,Bax mRNA表达量降低(P均<0.01)。TRAIL处理细胞后,下调了SGC7901/ADR细胞的MDR1、MRP1、Bcl-2 mRNA和蛋白的相对表达量,提高了Bax mRNA相对表达量,与空白对照相比,差异均有统计学意义(P均<0.05)。结论 TRAIL可能通过下调MDR1、MRP1、Bcl-2和上调Bax的表达促进胃癌耐药细胞的凋亡,进而部分逆转胃癌的多药耐药。To investigate the influence of tumor necrosis factor-related apoptosis-inducing ligand （TRAIL） on multidrug resistance gene （MDR1）, multidrug resistance-associated protein （MRP1）, anti-apoptotic gene Bcl-2 and pro-apoptotic gene Bax in human gastric cancer SGC7901/ADR cells and to explore the possible mechanism of TRAIL reversing multidrug resistance of gastric cancer.Methods The drug sensitivity of SGC7901/ADR cells and their parent cells SGC7901 to doxorubicin, vincristine and cisplatin was detected by MTT assay.The mRNA expression of MDR1, MRP1, Bcl-2, Bax gene of SGC7901/ADR and SGC7901 cells was detected by real-time fluorescence quantification PCR.SGC7901/ADR cells were treated with different concentrations of TRAIL （10, 50, 100 ng/mL）.The real-time fluorescence quantification PCR and Western blotting were used to measure the expression of MDR1, MRP1, Bcl-2, Bax mRNA and protein of various genes in different treatment groups and the blank control group.Results MTT assay for drug sensitivity test showed that, compared with SGC7901 cells, the IC50 of SGC7901/ADR cells to doxorubicin, vincristine and sisplatin was significantly increased （P〈0.01 or P〈0.05）.Compared with SGC7901, the expression levels of MDR1, MRP1, Bcl-2 mRNA in SGC7901/ADR cells were significantly increased, but the expression of Bax mRNA was decreased （all P〈0.01）.The mRNA and protein expression levels of MDR1, MRP1 and Bcl-2 in SGC7901/ADR cells were down-regulated by TRAIL, and the expression of pro-apoptotic protein Bax mRNA was up-regulated.Compared with the blank control group, there were statistically significant differences （all P〈0.05）.Conclusion TRAIL may down-regulate the expression of MDR1, MRP1, Bcl-2 and up-regulate the expression of Bax to promote the apoptosis of gastric cancer drug-resistant cells, and reverse multidrug resistance of gastric cancer drug-resistant cells.

关 键 词：胃肿瘤 肿瘤坏死因子相关凋亡诱导配体 多药耐药 细胞凋亡 

分 类 号：R735.2[医药卫生—肿瘤]