BIM缺失多态性与乳腺癌紫杉醇内源性耐药机制的关系  

Relationship between BIM deletion polymorphism and paclitaxel intrinsic resistance in breast cancer

作　　者：梁红玲 黄健清[2] 金田恩 李洪胜 姜明 陈忠生 兰卉 谭小军 

机构地区：[1]广州医科大学附属肿瘤医院,广州510095 [2]广州医科大学,广州510006 [3]广州达安临床检验中心,广州510520

出　　处：《实用医学杂志》2018年第4期531-534,共4页The Journal of Practical Medicine

基　　金：广东省卫计委指令性课题(编号:C2015039);广州市卫计委课题(编号:20151A011088);广州医科大学青年基金(编号:2014A35)

摘　　要：目的探讨BIM基因缺失多态性与乳腺癌紫杉醇内源性耐药机制的关系。方法采用PCR及基因测序筛查出具备BIM缺失多态性的人乳腺癌细胞株,再通过rt PCR、Western Blot、MTS等方法,检测其对紫杉醇的敏感性以及BIM m RNA、BIM蛋白的表达水平。结果T47D为BIM缺失多态性的人乳腺癌细胞株,相对野生型细胞株MCF7对紫杉醇药物敏感性显著较低[T47D vs.MCF-7,IC_(50)>30μmol/L vs.IC_(50)=(0.16±0.02)μmol/L];并且,T47D相对MCF7的BIM m RNA EXON3:EXON4比值明显增高而功能性BIM蛋白则表达下调(P<0.05)。结论BIM缺失多态性可能参与了乳腺癌紫杉醇内源性耐药机制。Objective The role of this essay is to explore the relationship of BIM deletion polymorphism and paclitaxel intrinsic resistance in breast cancer. Methods Human breast cancer cell lines were screened by techniques of PCR and gene sequencing to detect BIM deletion polymorphism. MTS was used to detect the cytotoxic effects of paclitaxel in different cell lines. Meanwhile, levels of BIM mRNA and protein were detected by rtPCR and Western Blot. Results Comparing with the wild type cell line （MCF7）, T47D was a deletion cell line with BIM deletion polymorphism and resistant to paclitaxel （T47D vs. MCF-7, IC50 〉 301e vs. IC50 = 0.16 vs. 02μmol/L）. Moreover, the ratio of BIM EXON3 to EXON4 was significantly increased and the level of functional BIM protein was down-regulated in T47D compared with MCF7 （P 〈 0.05）. Conclusion BIM deletion polymorphism might initiate intrinsic resistance to paclitaxel therapy in breast cancer.

关 键 词：乳腺癌 紫杉醇 耐药 BIM基因 

分 类 号：R737.9[医药卫生—肿瘤]