Synergistic effect of metformin on sorafenib in in vitro study using hepatocellular carcinoma cell lines

Annals of Hepato-biliary-pancreatic Surgery
Yong-Gyu ChungNayoung Kim

Abstract

Hepatocellular carcinoma (HCC) recurrence remains a great concern following hepatic resection and liver transplantation. We investigated the metformin-induced cytotoxic effects on sorafenib in an in vitro study using HCC cell lines. This research was conducted through an in vitro study using one HepG2.2.15 liver tumor and two patient-derived graft HCC cell lines. An in vitro study revealed noticeable cytotoxic effects of metformin as well as noticeable synergistic cytotoxic effects of metformin and sorafenib on cell viability. Assays for the mechanisms of action of antitumor effects revealed that alpha-fetoprotein expression was suppressed by both metformin and sorafenib, but no synergistic effect was observed. LC3-I and LC3-II assays revealed the synergistic upregulation of autophagy and assays for IL-1β, IL-6, p53, and TNF-α revealed the synergistic upregulation of cell damage and apoptosis. In contrast, metformin did not affect HBx expression, thus no noticeable synergistic effect was considered to be present. Our in vitro study demonstrated cytotoxic effects of metformin and synergistic antitumor effects of sorafenib. These results should be verified in further clinical studies with patients of advanced HCC.

References

Oct 26, 2006·Cancer Research·Mahvash ZakikhaniMichael Pollak
Oct 2, 2007·Trends in Molecular Medicine·Gary G Chiang, Robert T Abraham
Jul 25, 2008·The New England Journal of Medicine·Josep M LlovetUNKNOWN SHARP Investigators Study Group
Mar 25, 2010·Liver International : Official Journal of the International Association for the Study of the Liver·Valter DonadonGiorgio Zanette
May 7, 2010·Cell Metabolism·Adem KalenderGeorge Thomas
Jun 21, 2011·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Eric DavisMyron Schwartz
Jun 23, 2012·Pharmacogenetics and Genomics·Li GongTeri E Klein
Aug 2, 2014·International Journal of Cancer. Journal International Du Cancer·Floris H GroenendijkRené Bernards
Oct 30, 2015·Expert Opinion on Pharmacotherapy·Andrea Casadei GardiniGiovanni Luca Frassineti

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Citations

Apr 16, 2021·European Journal of Medicinal Chemistry·Deepika KathuriaPrasad V Bharatam
Jul 23, 2021·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Yiyin ChenNanhong Tang

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Methods Mentioned

BETA
xenograft
fluorescence microscopy
PCR
electrophoresis

Software Mentioned

SPSS
GraphPad Prism

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