Two-Step Process of Enzyme Inhibition and Drug Treatment Inhibits Liver Cancer Cell Growth in Lab Tests

Scientists at the University of Delaware (UD) and the University of Illinois at Chicago (UIC) have found a new way to kill liver cancer cells and inhibit tumor growth. First, they silence a key cellular enzyme, and then they add a powerful drug. They describe their methods in an open-access article published online on January 31, 2018 in Nature Communications. The article is titled “Hexokinase-2 Depletion Inhibits Glycolysis and Induces Oxidative Phosphorylation in Hepatocellular Carcinoma and Sensitizes to Metformin.” This research could accelerate the development of new treatments for liver cancer, which is currently difficult to cure. Often surgery is not an option for liver cancer, and the available drugs are only modestly effective. More than 82 percent of liver cancer patients die within five years of diagnosis, according to the National Institutes of Health. This project originated in labs at the UIC, where researchers grew liver cancer cells and manipulated their expression of an enzyme called hexokinase-2. Then, the cells were treated with metformin, a diabetes drug that decreases glucose production in the liver. The research group of Maciek R. Antoniewicz, PhD, Centennial Professor of Chemical and Biomolecular Engineering at the University of Delaware (UD), designed a set of experiments to measure how cancer cells respond to the loss of hexokinase-2, an enzyme that helps cells metabolize glucose, their food source. Dr. Antoniewicz is an expert in metabolic flux analysis, a technique for studying metabolism in biological systems. His research group is one of only a few in the world with expertise in a technique called 13C metabolic flux analysis of cancer cells, and he recently published a paper in Experimental & Molecular Medicine describing his methods.
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