格列卫增加获得性他莫昔芬耐受MCF-7细胞对阿霉素的敏感性  

Glivec enhances the down-regulated cytotoxicity of adriamycin in acquired tamoxifen-resistant MCF-7cell line

作　　者：王雄文[1] 张积仁[2] 沈雁[1] 郑刚[2] 钟灿灿[1] 

机构地区：[1]暨南大学第四附属医院老年科,广东广州510220 [2]第一军医大学珠江医院肿瘤科,广东广州510280

出　　处：《第一军医大学学报》2003年第7期731-733,共3页Journal of First Military Medical University

摘　　要：目的探讨获得性他莫昔芬(TAM)耐受MCF-7细胞bax、bcl-2、p170表达的变化及其对阿霉素(ADR)敏感性的影响。方法流式细胞术检测MCF-7及经1×10-7 mol/L TAM持续作用8、16周的MCF-7细胞bax、bcl-2、p170的表达变化;三磷酸腺苷发光法检测TAM处理后的MCF-7对ADR药敏的变化及格列卫(Glivec)对ADR药敏的影响;流式细胞术检测细胞内ADR的固有荧光强度。结果获得性TAM耐受MCF-7细胞p170表达阳性率由父代的(27.43±2.16)%上升到(32.13±1.31)%(P<0.05),bcl-2由父代的(41.53±2.17)%下降到(37.87±1.86)%(P>0.05),bax则由父代的(53.17±1.45)%下降到(28.70±1.41)%(P<0.01)。同时,10 μg/ml格列卫可使耐受TAM的MCF-7细胞内ADR荧光强度增加(P<0.05)。结论获得性耐受TAM的MCF-7细胞对ADR敏感性降低的原因之一可能是由于bax表达明显降低及p170表达增高,合用格列卫可增强耐受TAM的MCF-7对ADR的细胞毒性作用。Objective To study the alteration of bax, bcl-2, p170 expressing and the second effect on the adriamycin (ADR) induced cytotoxicity in acquired tamoxifen (TAM)-resistant MCF-7 cell line. Methods The bax, bcl-2, p170 protein expressions were detected by flow cytometry respectively, as well as the content of intracellular ADR. The in vitro adenosine triphosphate tumor chemosensitivity assay (ATP-TCA) was performed to evaluate the cytotoxicity of ADR, and also the effect of Glivec on the cytotoxicity of ADR. Results The percentages of bax, bcl-2 expressions in the acquired TAM resistant MCF-7 were down-regulated from 53.17±1.45% to 28.70±1.41% (P<0.01), 41.53±2.17% to 37.87±1.86%(P>0.05)respectively, the p170 was up-regulated from 27.43±2.16% to 32.13±1.31% (P<0.05), after a 16-week-treatment with 1×10 -7 mol/L TAM. Accordingly, the chemosensitivity and the fluorecence intensity of intracellular ADR declined, both of them can be significantly reversed by 10 μg/ml Glivec. Conclusions The acquired TAM resistant MCF-7 companied with a declined ADR cytotoxicity, down-regulation of bcl-2/bax-induced apoptosis and up-regulation of p170-induced drug efflux may had a synergic devotion. Glivec may enhance the cytotoxicity of ADR on the acquired TAM-resistant MCF-7 cell line.

关 键 词：乳腺肿瘤 格列卫 他莫昔芬 阿霉素 敏感性 流式细胞术 

分 类 号：R730.5[医药卫生—肿瘤]