Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University No. 83 Xiqiaozheng Street, Chongqing 400037, China.
Am J Transl Res. 2015 Jan 15;7(1):88-99. eCollection 2015.
The efficacy of chemotherapy in patients with hepatocellular carcinomas still poor due to multidrug resistance. This study aimed to investigate the impact of the over-expressed mitochondrial human telomerase reverse transcriptase on multidrug resistance of hepatocellular carcinomas.
HepG2 and SK-Hep1 cell lines were used. And sensitivity to chemotherapeutic drugs was detected.
Mitochondrial human telomerase reverse transcriptase over-expression in hepatocellular carcinomas cells could significantly reduce its sensitivity to multiple chemotherapeutic drugs in vitro and in vivo. Hepatocellular carcinomas cells over-expressing mitochondrial human telomerase reverse transcriptase showed a significantly higher mitochondrial membrane potential, a markedly lower activated caspase-3 after drug treatment, and an increased mtDNA copy number, which explained the drastically decreased drug-induced apoptosis of hepatocellular carcinomas cells with mitochondrial human telomerase reverse transcriptase over-expression.
Over-expressed mitochondrial human telomerase reverse transcriptase may increase the mtDNA copy number and inhibit the activation of mitochondrial apoptotic pathway to contribute to the multidrug resistance of hepatocellular carcinomas cells.
由于多药耐药性，化疗在肝细胞癌患者中的疗效仍然不佳。本研究旨在探讨过度表达的线粒体人端粒酶逆转录酶对肝癌多药耐药性的影响。
使用 HepG2 和 SK-Hep1 细胞系。并检测对化疗药物的敏感性。
肝癌细胞中线粒体人端粒酶逆转录酶的过度表达可显著降低其在体外和体内对多种化疗药物的敏感性。过表达线粒体人端粒酶逆转录酶的肝癌细胞表现出明显更高的线粒体膜电位，药物处理后激活的 caspase-3 明显降低，以及 mtDNA 拷贝数增加，这解释了线粒体人端粒酶逆转录酶过度表达导致肝癌细胞中药物诱导的凋亡明显减少。
过度表达的线粒体人端粒酶逆转录酶可能会增加 mtDNA 拷贝数并抑制线粒体凋亡途径的激活，从而导致肝癌细胞的多药耐药性。
