Abstract
Sorafenib, the first-line agent for treatment of advanced hepatocellular carcinoma (HCC), improves median overall survival by approximately 3months. In the present study, we investigated whether sorafenib combined with cucurbitacin B (CuB), a natural tetracyclic triterpenoid isolated from Cucurbitaceae, exerts enhanced antitumor effects against HCC. Cell viability and colony formation ability were detected by cell-counting kit-8 and colony formation assays. Cell cycle and apoptosis were analyzed by flow cytometry. Protein expression was detected by western blotting. HepG2 xenografts in nude mice were used to evaluate invivo antitumor effects. We report that sorafenib and CuB exhibited synergistic effects on cellular proliferation inhibition and cell apoptosis induction, but not on cell cycle arrest. Furthermore, combination treatment enhanced levels of cleaved caspase 3 and cleaved caspase 9, but suppressed phosphorylation of STAT3. Epidermal growth factor, a potent stimulator of signal transducer and activator of transcription-3 (STAT3), promoted cell viability and colony formation ability, whereas combination treatment exerted inhibitory effects on epidermal growth factor-induced STAT3 phosphorylation. Finally, HepG2 xenograft mice cotreated with sorafenib and CuB exhibited reduced tumor progression without notable weight loss. In conclusion, sorafenib and CuB exert synergistic antitumor effects through a pathway that may involve STAT3 phosphorylation, and this may represent a promising therapeutic approach for treatment of HCC.
Highlights
Hepatocellular carcinoma is the fifth most commonly diagnosed cancer and the third leading cause of cancer-related death worldwide [1]
FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies
The synergistic antiproliferative effects of sorafenib combined with Cucurbitacin B (CuB) in hepatocellular carcinoma (HCC) cells To investigate the antiproliferative effects of sorafenib and/or CuB in HCC cells, HepG2, Huh7 and Hep3B cells were treated with increasing concentrations of agents, alone and in combination
Summary
Hepatocellular carcinoma is the fifth most commonly diagnosed cancer and the third leading cause of cancer-related death worldwide [1]. The common causes of hepatocellular carcinoma (HCC) are attributed to chronic infection by hepatitis B or C virus infection, alcohol abuse, metabolic syndrome and non-alcoholic fatty liver diseases [2,3]. Sorafenib is the first multikinase inhibitor approved by the Food and Drug Administration for treatment of advanced HCC in 2007 by targeting the RAF/MEK/ERK pathway and tyrosine kinases vascular endothelial growth factor receptor/platelet-derived growth factor receptor [6,7]. It is imperative to investigate other effective agents to combine with sorafenib with the aim of improving antitumor therapeutic effects and suppressing disease progression in the management of hepatocellular carcinoma
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
