Metformin attenuates hepatoma cell proliferation by decreasing glycolytic flux through the HIF-1α/PFKFB3/PFK1 pathway

Publication date: Available online 15 October 2019Source: Life SciencesAuthor(s): La Hu, Zicheng Zeng, Qing Xia, Zhaoyu Liu, Xiao Feng, Jitao Chen, Mengqiu Huang, Liangcai Chen, Zhiyuan Fang, Qiuzhen Liu, Hongbo Zeng, Xinke Zhou, Jifang LiuAbstractAimsEnhanced 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. However, the underlying molecular mechanism of its action linking glucose metabolism with the suppression of proliferation has not been fully clarified.Main methodsStable isotope tracing technology and gas chromatography–mass spectrometry method were utilized to analyze the effect of metformin on glycolytic flux in HCC cells. Western blot and immunohistochemistry were utilized to analyze the expression of phosphofructokinase-1 (PFK1) and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) in HCC cells or xenograft tumor tissures. Lactate measurement and glucose uptake assay were used to analyze the level of lactate and glucose in the presence of frucose-2,6-diphosphate (F2,6BP) in HCC cells treated with metformin.Key findingsWe 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 ...
Source: Life Sciences - Category: Biology Source Type: research