紫杉醇耐药人卵巢癌细胞株中线粒体DNA基因突变的研究  

The research for mitochondrial DNA mutation in ovary cancer Taxol-resistant cell line

作　　者：赵晋[1] 李红霞[1] 张素梅[1] 

机构地区：[1]首都医科大学附属北京世纪坛医院妇产科,北京100038

出　　处：《现代妇产科进展》2012年第6期478-481,共4页Progress in Obstetrics and Gynecology

基　　金：国家863子课题肿瘤生物学与癌标志物研究资助(No:2006AA02A245)

摘　　要：目的:研究紫杉醇耐药的人卵巢癌细胞株SKOV3/Tax和OC3/Tax中线粒体DNA(mtDNA)突变。方法:提取细胞DNA,分析mtDNA突变,比较SKOV3/Tax和OC3/Tax与亲本敏感细胞SKOV3及OC3之间mtDNA突变数量和突变类型的差异。结果:紫杉醇耐药及敏感细胞mtDNA的突变热点依次是ND5基因、Cytb基因、ND4基因、CoⅡ基因及ND1基因;与敏感细胞株相比,耐药细胞株中mtDNA测序中发现更多的基因突变频率,主要表现为A→C,A→G,T→C,A→T,缺失A、C,插入T、C等,其中以缺失A最为明显。结论:人卵巢癌细胞株OC3及SKOV3中mtDNA编码区的ND5基因、Cytb基因、ND4基因和CoⅡ基因是具有高度突变性的区域,其与卵巢癌的发生、发展有重要关系。耐药细胞株中的突变明显高于敏感细胞株,推测突变的增加可能与卵巢癌耐药有关。Objective：To explore the mtDNA mutation in ovary cancer Taxol-resistant cell line SKOV3/Tax and OC3/Tax.Methods：mtDNA were extracted and gene sequencing were done in Ovary Cancer Taxol-resistant Cell Line SKOV3/Tax and OC3/Tax,compared with their parental cell SKOV3 and OC3（sensitive line）.The difference of mtDNA mutation rate and type were analyzed between them.Results：The hot point mutation in mtDNA coding region were ND5 gene,Cytb gene,ND4 gene,Co Ⅱ gene and ND1 gene in subsequently.Compare with the sensitive cell lines,there were more changes in genetic mutations in drug-resistent ones.The main mutation types were A→C,A→G,T→C,A→T,lost A/C,insert T/C.Lost A is the remarkable characteristics.Conclusions：The mtDNA gene of ND5,Cytb,ND4,CoⅡ are the highly mutation region in ovary cancer cell line both in Taxol-resistant cell lines and their parental lines,that may be have some relations with ovary carcinogenesis and development.MtDNA mutation in drug-resistent cell lines have more marked difference than in the sensitive lines,indicating that may be related with the mechanism of Taxol-resistance in ovarian cancer.

关 键 词：卵巢肿瘤 DNA 线粒体 突变 抗药性 肿瘤 人卵巢癌细胞株 紫杉醇耐药 

分 类 号：R737.33[医药卫生—肿瘤]