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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。
AIM: To investigate the mitochondrial DNA (mtDNA) mutations in paclitaxel-resistant human ovarian cancer cell lines SKOV3 / Tax and OC3 / Tax. Methods: DNA was extracted and mtDNA mutations were analyzed. The number of mtDNA mutations and the types of mutations were compared between SKOV3 / Tax and OC3 / Tax and their parental SKOV3 and OC3 cells. Results: The mutational hot spots of mtDNA of paclitaxel resistant and sensitive cells were ND5 gene, Cytb gene, ND4 gene, Co Ⅱ gene and ND1 gene respectively. Compared with sensitive cell lines, more gene mutations were found in mtDNA sequencing of drug resistant cell lines Frequency, the main manifestations of A → C, A → G, T → C, A → T, A, C, insert T, C and so on, of which the most obvious deletion A. Conclusion: The ND5 gene, Cytb gene, ND4 gene and Co Ⅱ gene in mtDNA coding region of human ovarian cancer cell lines OC3 and SKOV3 are highly mutated regions, which are closely related to the occurrence and development of ovarian cancer. Mutations in drug-resistant cell lines were significantly higher than those in sensitive cell lines, suggesting that increased mutations may be related to drug resistance in ovarian cancer.