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Metformin Inhibits Angiogenesis Induced by Interaction of Hepatocellular Carcinoma with Hepatic Stellate Cells

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Abstract

Accumulated evidences indicate metformin is associated with reduced risk of hepatocellular carcinoma (HCC) in diabetic patients, which inspired researchers to explore its therapeutic potentials in HCC. Since Hepatic stellate cells (HSCs) are believed to be the key contributors to tumor microenvironment in HCC and promotes tumor development, here, we explored the effect of metformin on tumor angiogenesis induced by interplay of HCC and HSCs. Our results showed that conditional medium from co-culture of HCC/HSCs induced VEGF secretions and stimulated human umbilical vein endothelial cells (HUVEC) tube formation. However, 25 µM metformin could inhibit this angiogenesis effect. Furthermore, knockdown AMPK of HSCs, not HCC, could abolish inhibition caused by metformin. Our finding suggested that metformin could inhibit HCC angiogenesis through targeting on HSCs through AMPK pathway.

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Authors and Affiliations

  1. Department of Gastroenterology, Weifang People’s Hospital, 151 Guangwen Street, Kuiwen District, Weifang, 261041, Shangdong, People’s Republic of China

    Hongmei Qu

  2. Department of Surgery, People’s Hospital of Linzi District, Affiliated to Binzhou Medical College, Zibo, 255400, Shandong, People’s Republic of China

    Xingwang Yang

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  1. Hongmei Qu
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Correspondence to Xingwang Yang.

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Qu, H., Yang, X. Metformin Inhibits Angiogenesis Induced by Interaction of Hepatocellular Carcinoma with Hepatic Stellate Cells. Cell Biochem Biophys 71, 931–936 (2015). https://doi.org/10.1007/s12013-014-0287-8

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  • DOI: https://doi.org/10.1007/s12013-014-0287-8

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