胶质瘤SP细胞耐药靶分子ABCG2的实验研究

Experimental Study on the Drug Resistance Gene ABCG2:a Marker of Small Population Cells

背景与目的:ABCG2是ATP转运蛋白(ATP binding cassette,ABC)家族中G2成员,具有编码乳腺癌耐药蛋白(breast cancer resistance protein,BCRP)功能,在肿瘤研究中又可作为SP细胞标志蛋白来筛选肿瘤干细胞,本研究旨在逆转其耐药作用。方法:尼卡地平(NCDP)、尼莫司汀(ACNU)分别和联合作用于人脑多形性胶质母细胞瘤(GBM)体外细胞系和裸小鼠脑移植瘤。体外实验:用MTT比色法检测药物作用后GBM细胞存活率,流式细胞仪检测细胞凋亡率;体内实验:观察荷瘤裸小鼠的生存期及移植瘤病理。结果:体外实验中,AC-NU+NCDP组对肿瘤抑制和促进凋亡作用都显著高于ACNU组(P<0.01)。体内实验中,ACNU+NCDP组的生存期比ACNU组明显延长(P<0.01)。结论:随着胶质瘤恶性程度增高而表达率增加的ABCG2耐药基因功能因被NCDP抑制后增强了ACNU对胶质瘤细胞的杀伤、促进凋亡和延长荷瘤鼠生存期的作用。

BACKGROUND ＆ OBJECTIVE：ABCG2 （the G2 member of ATP-binding cassette family）, which encodes breast cancer resistance protein （BCRP）, is regarded as a marker of small population （SP）cells to identify tumor stem cells. This paper aimed at study of the inhibition of resistance to chemotherapeutic drugs. METHODS： Ghobastoma multfforme （GBM） cells and nude mice burdened with xenografts of GBM were treated with ACNU, NCDP or both of the drugs respectively. In vitro, MTT assay was performed to evaluate the inhibitory effects on proliferation of GBM ceils. The apoptotic rate of GBM ceils was estimated by flow cytometry （FCM）. In vivo, survival time of these nude mice was assessed and the pathology of implanted xenografts were analyzed. RESULTS： In vitro, the inhibition rate and apoptotic rate of GBM in the group of NCDP＋ACNU combined administration were significantly higher than that of single agent administration of ACNU and control group （P〈 0.01）. In vivo, the survival of nude mice of combined administration of ACNU and NCDP was markedly prolonged when compared with those given the single agent ACNU （P〈0.01）. CONCLUSION： The inhibition of drug resistance gene ABCG2 by NCDP could enhance the cytotoxicity of ACNU, promote apoptosis and might prolong survival of nude mice bearing tumors.