BACKGROUND: 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. METHODS: HepG2 and SK-Hep1 cell lines were used. And sensitivity to chemotherapeutic drugs was detected. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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. METHODS: HepG2 and SK-Hep1 cell lines were used. And sensitivity to chemotherapeutic drugs was detected. RESULTS: 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. CONCLUSION: 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.
Authors: Chiara Mondello; Maria Grazia Bottone; Sakon Noriki; Cristiana Soldani; Carlo Pellicciari; Anna Ivana Scovassi Journal: Ann N Y Acad Sci Date: 2006-12 Impact factor: 5.691
Authors: Kenkichi Masutomi; Richard Possemato; Judy M Y Wong; Jennifer L Currier; Zuzana Tothova; Judith B Manola; Shridar Ganesan; Peter M Lansdorp; Kathleen Collins; William C Hahn Journal: Proc Natl Acad Sci U S A Date: 2005-05-31 Impact factor: 11.205
Authors: Y Shang; Z Zhang; Z Liu; B Feng; G Ren; K Li; L Zhou; Y Sun; M Li; J Zhou; Y An; K Wu; Y Nie; D Fan Journal: Oncogene Date: 2013-07-29 Impact factor: 9.867
Authors: Theresa M Wardell; Elaine Ferguson; Patrick F Chinnery; Gillian M Borthwick; Robert W Taylor; Graham Jackson; Alan Craft; Robert N Lightowlers; Neil Howell; Douglass M Turnbull Journal: Mutat Res Date: 2003-04-09 Impact factor: 2.433