分化抑制因子1表达对膀胱癌细胞系化疗敏感性及细胞凋亡的影响  

Id-1 expression regulate bladder cancer cell line chemosensitivity and apoptosis

作　　者：胡浩[1] 许克新[1] 王驭良[1] 张晓鹏[1] 于路平[1] 王晓峰[1] 

机构地区：[1]北京大学人民医院泌尿外科,100044

出　　处：《现代泌尿生殖肿瘤杂志》2010年第5期220-224,共5页Journal of Contemporary Urologic and Reproductive Oncology

摘　　要：目的探讨分化抑制因子1(inhibitor of differentiation,Id-1)下调对膀胱癌细胞系化疗敏感性及药物诱导细胞凋亡的影响。方法选取膀胱上皮癌细胞系MGH-U1,在构建Id-1si-RNA载体后,通过逆转录病毒将其转染至MGH-U1细胞,筛选出稳定低表达Id-1的克隆(si-Id-1)和对照载体克隆(sscon)。MTT法和集落形成实验比较sscon细胞和si-Id-1克隆细胞对表柔比星的敏感性;Ⅰ型胶原侵袭实验证明Id-1下调对膀胱癌细胞侵袭能力的影响;Western blot实验检测凋亡相关蛋白,比较凋亡蛋白表达水平,研究Id-1下调对表柔比星诱导的细胞凋亡的影响。结果 si-Id-1克隆细胞对表柔比星的敏感性显著高于sscon细胞;si-Id-1克隆细胞的侵袭能力明显低于sscon细胞;Id-1下调会诱导凋亡通路激活因子Cleaved PARP和Cleaved Caspase3的表达水平增高,从而证明Id-1下调会增加表柔比星诱导的细胞凋亡。结论膀胱癌细胞Id-1下调可以增加抗肿瘤药物诱导的细胞凋亡,从而增加肿瘤细胞的化疗敏感性。Objective To investigate the down regulation of inhibitor of differentiation-1 （Id-1） impacted on the chemosensitivity and the chemotherapeutic drug induced apoptosis of bladder cancer cells.Methods The Id-1 si-RNA vector was generated and transfected into MGH-U1 cells.Stable si-Id-1 transfectants and vector control clones were generated.MTT assay and colony forming assy were performed to compare the chemosensitivity of si-Id-1 transfectants and vector control.Type Ⅰ collagen invasion assay was used to detect the invasive ability of different clones.The expression levels of apoptosis related proteins were analyzed by Western blot to study the effect of Id-1 suppression on chemotherapeutic drug-induced apoptosis.Results After generation of the stable Id-1 down-regulation transfectants successfully,the results of MTT assay and colony forming assay showed down-regulation of Id-1 could increase cellular sensitivity to epirubicin.Type Ⅰ collagen invasion assay showed less percentage of the si-Id-1 cells than vector cells could invade into extracellular matrix.Furthermore,the analysis of apoptosis related protein revealed that down-regulation of Id-1 leaded to increased expression of cleaved PARP and cleaved Caspase 3,which support the negative role of Id-1 in epirubicin induced apoptosis.Conclusion s This study suggested that down-regulation of Id-1 could increase the chemotherapeutic drug induced apoptosis and get better cellular chemosensitivity.

关 键 词：ID-1 化疗敏感性 细胞凋亡 

分 类 号：R737.14[医药卫生—肿瘤]