腺病毒介导的靶向自杀基因对卵巢癌耐药细胞株的杀伤作用  

Killing Effects of Adenovirus Mediated mdr1-CD∷UPP Gene on Resistant Ovarian Cancer

作　　者：卢实[1] 孙敬霞[1] 王晓翊[1] 肖蓝[1] 王泽华[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院妇产科,武汉430022

出　　处：《华中科技大学学报（医学版）》2007年第4期492-494,共3页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.30070786)

摘　　要：目的研究多药耐药基因1(mdr1)调控的胞嘧啶脱氨酶-尿嘧啶磷酸核糖转移酶融合基因(CD∷UPP)联合5-氟胞嘧啶(5-FC)后对卵巢癌紫杉醇耐药细胞株生长的影响。方法以复制缺陷型重组腺病毒为载体,将mdr1-CD∷UPP基因分别转染2对人卵巢癌紫杉醇耐药细胞株A2780/Taxol、SKOV3/Taxol及非耐药细胞株A2780和SKOV3,加入含5-FC的培养液培养,5 d后噻唑蓝(MTT)法检测细胞存活率,观察旁观者效应。结果5-FC对转基因耐药细胞的生长抑制作用明显高于转基因的非耐药细胞,随着5-FC浓度增加,抑制作用增强;通过旁观者效应5-FC可杀伤周围未转基因的耐药细胞。结论mdr1-CD∷UPP靶向自杀基因联合5-FC后对紫杉醇耐药细胞具有显著的特异性杀伤作用。Objective To observe the specific killing effects of adenovirus-mediated mdrl-CD∷UPP gene driven by mdrl promoter with 5-fluorocytosine （5-FC） on Taxol-resistant ovarian cancer cells. Methods Taxol-resistant （A2780/Taxol, SKOV3/Taxol） and Taxol-sensitive （A2780, SKOV3） ovarian cancer cells were transfected with mdrl-CD∷UPP gene by adeno virus vector and cultured with culture medium containing 5-FC. MTT assays were performed to test the viability of cells and stander-by effects were observed. Results Taxol-resistant cells transfeeted with mdrl-CD∷UPP gene expressed an extraordinary sensitivity to 5-FC compared with Taxol-sensitive cells. Mixed cells assay revealed that 20%0 CD∷UPP positive cells could kill about 80% mixed cells by stander-by effects. Conclusion Adenovirus-mediated mdr1-CD∷UPP gene driven by mdr1 promoter could confer selective killing on Taxol-resistant ovarian cancer cells.

关 键 词：卵巢癌 基因治疗 多药耐药 

分 类 号：R737.31[医药卫生—肿瘤]