膜微粒对P-糖蛋白和多药耐药基因1转移的影响  

Effects of membrane microparticles on transference of P-glycoprotein and multidrug-resistance gene 1

作　　者：张珦 赖仁胜 许文林[2] 房新建[3] 

机构地区：[1]南京中医药大学附属医院病理科,江苏省210029 [2]江苏大学附属人民医院中心实验室 [3]连云港市第二人民医院肿瘤内科

出　　处：《江苏医药》2013年第24期2965-2968,I0001,共5页Jiangsu Medical Journal

基　　金：江苏高校优势学科建设工程一期项目

摘　　要：目的探讨多药耐药白血病细胞株VLB100提取物-膜微粒介导P-糖蛋白(P-gp)及其编码基因多药耐药基因1(MDR-1)的转移以及对亲代敏感细胞株CCRF-CEM细胞耐药性的影响。方法从VLB100细胞中提取膜微粒,将其与CCRF-CEM细胞共培养。RT-PCR和流式细胞术分别检测MDR-1基因和P-gp的表达,罗丹明123(Rh123)滞留试验检测P-gp功能,MTT法检测膜微粒对阿霉素细胞毒作用的影响。结果膜微粒处理后,CCRF-CEM细胞MDR-1基因及P-gp表达水平增加(P<0.05),细胞内的Rh123积聚减少(P<0.05),细胞对阿霉素的耐药性增加(P<0.05),且均呈剂量依赖性。而多药耐药蛋白1(MRP1)及乳腺癌耐药蛋白(BCRP)基因的表达在处理前后无明显变化(P>0.05)。结论膜微粒可诱导MDR-1基因及P-gp转移,增加CCRF-CEM细胞对阿霉素的耐药性。Objective To investigate the effects of membrane microparticles extracted from multidrug-resistant tumor cells VLB100 on the transference of multidrug-resistance gene I（MDR-1） and its protein product P-glycoprotein（P-gp） and drug sensitivity of CCRF-CEM cell lines. Methods Membrane microparticles were extracted from VLB100 cells and added to CCRF-CEM cell culture. The expressions of MDR-1 and P-gp were detected by RT-PCR and flow cytometry, respectively. The biological activity of P-gp was examined by rhodamine 123 （Rh123） retention assay. The effect of membrane microparticles on cytotoxicity of adriamyein in CCRF-CEM ceils was detected by MTT assay. Results The expression levels of MDR-1 and P-gp were increased（P〈0. 05）, the accumulation of Rh123 was decreased （P〈0. 05）, and drug resistance to adriamycin was increased （P〈0. 05） in CCRF-CEM cells after treated with membrane microparticles in a dose-dependent manner. However, the expression levels of MRP1 and BCRP genes had no significant difference after treated with membrane micropartieles. Conclusion Membrane microparticles extracted from VLB100 cells are able to induce the transference of MDR-1 gene and P-gp to drug-sensitive cells and increase the resistance of CCRF-CEM cells to adriamycin.

关 键 词：膜微粒 P-糖蛋白 多药耐药基因1 

分 类 号：R730[医药卫生—肿瘤]