Hu, La published the artcileMetformin attenuates hepatoma cell proliferation by decreasing glycolytic flux through the HIF-1α/PFKFB3/PFK1 pathway, Related Products of alcohols-buliding-blocks, the main research area is hepatoma cell metformin glycolytic flux HIF1 alpha PFKFB3 PFK1; Glycolytic flux; Hepatocellular carcinoma; Metformin; PFK1.
Enhanced aerobic glycolysis is an essential hallmark of malignant cancer. Blocking the glycolytic pathway has been suggested as a therapeutic strategy to impair the proliferation of tumor cells. Metformin, a widely used anti-diabetes drug, exhibits anti-tumor properties. Stable isotope tracing technol. and gas chromatog.-mass spectrometry method were utilized to analyze the effect of metformin on glycolytic flux in HCC cells. Western blot and immunohistochem. were utilized to analyze the expression of phosphofructokinase-1 and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 in HCC cells or xenograft tumor tissues. Lactate measurement and glucose uptake assay were used to analyze the level of lactate and glucose in the presence of frucose-2,6-diphosphate in HCC cells treated with metformin. We found that metformin significantly impaired hepatoma cell proliferation by inhibiting the glycolytic flux via PFK1 blockade. Interestingly, activation of PFK1 by F2,6BP reverses the inhibitory effect of metformin on hepatoma cell proliferation and glycolysis. Mechanistically, PFKFB3,a potent allosteric activator of PFK1, was markedly suppressed through inhibiting hypoxia-induced factor 1 accumulation mediated by metformin. Taken together these data indicate that HIF-1α/PFKFB3/PFK1 regulatory axis is a vital determinant of glucose metabolic reprogramming in hepatocellular carcinoma, which gives new insights into the action of metformin in combating liver cancer.
Life Sciences published new progress about Cell proliferation. 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, Related Products of alcohols-buliding-blocks.
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