胃癌SGC7901/OXA细胞耐药与侧群细胞比例及Mdr1、ERCC1基因表达的关系  

Relationship of cellular drug resistance to proportion of side population cells and expression of Mdr1 and ERCC1in human gastric cell line SGC7901/OXA

作　　者：陈刚[1] 王清睿[1] 邱红[1] 柯善栋[1] 向莹[1] 胡少明[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院,湖北省武汉市430030

出　　处：《世界华人消化杂志》2011年第12期1219-1224,共6页World Chinese Journal of Digestology

基　　金：湖北省卫生厅科研基金资助项目;No.JX3B13~~

摘　　要：目的:探讨胃癌耐药细胞系SGC7901/OXA获得性耐药的发生机制.方法:利用间歇增加剂量方法诱导成功的SGC7901/OXA细胞株作为观察组,亲代细胞株SGC7901为对照组,采用MTT的方法观察OXA对两组的抑制率,计算IC50和耐药指数(RI);采用RT-PCR和Westernblot的方法分别检测两组多药耐药1(Mdr1)mRNA浓度和切除修复交叉互补基因组1(ERCC1)的蛋白浓度;采用流式细胞仪检测两组细胞中侧群(SP)细胞的比例.结果:SGC7901/OXA细胞各浓度抑制率较SGC7901明显降低,两者IC50分别为38.23μmol/L和7.12μmol/L,RI为5.37;Mdr1mRNA与β-actinmRNA光密度比值在两组中分别为0.468±0.147和0.427±0.136(n=5),两者差异无明显统计学意义(P=0.079);ERCC1蛋白浓度在SGC7901/OXA细胞较SGC7901细胞中明显增加;SGC7901中SP细胞的比例为1.8%,SGC7901/OXA中SP细胞的比例达到了6.1%,较SGC7901细胞明显升高(P<0.05).结论:SGC7901/OXA较SGC7901对OXA明显耐药,其获得性耐药的机制可能与ERCC1蛋白浓度以及SP细胞比例的变化有关,而Mdr1基因的作用不明显.AIM： To investigate the mechanism of acquired drug resistance in human gastric cancer cell line SGC7901/OXA.METHODS： SGC7901/OXA cell line was ob-tained by exposure of SGC7901 cells to increas-ing doses of oxaliplatin （OXA）. The parental cell line SGC7901 was used as a control. The reduced rate of cell growth, half maximal inhibitory concentration （IC50）, and resistance index （RI） were measured by MTT assay and compared between the two groups of cells. The expression of multidrug resistance 1 （Mdr1） mRNA and excision repair cross-complementing group 1 （ERCC1） protein was detected by RT-PCR and Western blot, respectively. The proportion of side population （SP） cells was determined by flow cytometry.RESULTS： The reduced rate of cell growth significantly decreased and IC50 increased （38.23 μmol/L vs 7.12 μmol/L） in SGC7901/OXA cells compared to parental SGC7901 cells. The RI was 5.37 in SGC7901/OXA cells. There was no significant difference in the relative expression level of Mdr1 mRNA （0.468 ± 0.147 vs 0.427 ± 0.136, P = 0.079） between the two groups. ERCC1 protein level was signifi cantly higher in SGC7901/OXA cells than in SGC7901 cells. The proportion of SP cells was also signifi cantly higher in SGC7901/OXA cells than in SGC7901 cells （6.1% vs 1.8%, P 0.05）.CONCLUSION： SGC7901/OXA cells were more signif icantly resistant to OXA than SGC7901. The mechanism of acquired resistance of SGC7901/OXA cells may be associated with changes in ERCC1 protein expression and proportion of SP cells.

关 键 词：胃肿瘤 耐药 侧群细胞 切除修复交叉互补基因组 多药耐药1 

分 类 号：R735.2[医药卫生—肿瘤]