By a News Reporter-Staff News Editor at Gene Therapy Weekly -- Current study results on Small Interference RNAs (siRNAs) have been published. According to news reporting out of Taipei, Taiwan, by NewsRx editors, research stated, "Sorafenib is the only drug approved for the treatment of hepatocellular carcinoma (HCC). The bioenergetic propensity of cancer cells has been correlated to anticancer drug resistance, but such correlation is unclear in sorafenib resistance of HCC."
Our news journalists obtained a quote from the research from National Taiwan University, "Six sorafenib-naive HCC cell lines and one sorafenib-resistant HCC cell line (Huh-7R; derived from sorafenib-sensitive Huh-7) were used. The bioenergetic propensity was calculated by measurement of lactate in the presence or absence of oligomycin. Dichloroacetate (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor, and siRNA of hexokinase 2 (HK2) were used to target relevant pathways of cancer metabolism. Cell viability, mitochondrial membrane potential, and sub-G1 fraction were measured for in vitro efficacy. Reactive oxygen species (ROS), adenosine triphosphate (ATP) and glucose uptake were also measured. A subcutaneous xenograft mouse model was used for in vivo efficacy. The bioenergetic propensity for using glycolysis correlated with decreased sorafenib sensitivity (R(2)=0.9067, among sorafenib-naive cell lines; p=0.003, compared between Huh-7 and Huh-7?R). DCA reduced lactate production and increased ROS and ATP, indicating activation of oxidative phosphorylation (OXPHOS). DCA markedly sensitised sorafenib-resistant HCC cells to sorafenib-induced apoptosis (sub-G1 (combination vs sorafenib): Hep3B, 65.4±8.4% vs 13±2.9%; Huh-7?R, 25.3± 5.7% vs 4.3±1.5%; each p
According to the news editors, the research concluded: "The bioenergetic propensity is a potentially useful predictive biomarker of sorafenib sensitivity, and activation of OXPHOS by PDK inhibitors may overcome sorafenib resistance of HCC."
For more information on this research see: Activating oxidative phosphorylation by a pyruvate dehydrogenase kinase inhibitor overcomes sorafenib resistance of hepatocellular carcinoma. British Journal of Cancer, 2013;108(1):72-81. (Nature Publishing Group - www.nature.com/; British Journal of Cancer - www.nature.com/bjc/)
Our news journalists report that additional information may be obtained by contacting Y.C. Shen, Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan. Additional authors for this research include D.L. Ou, C. Hsu, K.L. Lin, C.Y. Chang, C.Y. Lin, S.H. Liu and A.L Cheng (see also Small Interference RNAs (siRNAs)).
Keywords for this news article include: Asia, Biotechnology, Taipei, Taiwan, Kinase, Genetics, Oncology, Pyruvates, Keto Acids, Oil and Gas, Bioenergetics, Dehydrogenase, Bioengineering, Enzymes and Coenzymes, Hepatocellular Carcinoma, Small Interference RNAs (siRNAs).
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