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Abstract
Sorafenib, an oral multiple kinase inhibitor, is the standardized treatment for hepatocellular carcinoma (HCC). It is associated with severe adverse events that compromise its use. Controlling adverse events through dose reduction can enhance drug adherence and treatment response. One strategy to improve HCC therapy is to combine agents that target key signaling pathways. We set out to investigate the effect of a combination of sorafenib with either bevacizumab (anti-VEGF), panitumumab (anti- EGFR) or ramucirumab (anti-VEGFR2) monoclonal antibodies, in terms of improved efficacy and possibility of therapeutic dose reduction of sorafenib. HepG2 cancer cell line was treated with sorafenib alone or in combination with either bevacizumab, panitumumab or ramucirumab. A cytotoxicity assay was performed to determine the effect of different treatments on cell viability. Apoptosis and cell cycle distribution, the relative gene expression of VEGFR2, EGFR, MMP-9 and CASPASE3, the protein levels of pVEGFR2 and pSTAT3 and the protein expression of CASPASE3, EGFR and VEGFR2 in treated HepG2 cells were also determined. A cytotoxic effect was detected following treatment of HepG2 cancer cell line with sorafenib; the calculated IC50 of sorafenib was 17.2 at 24h, 10.5 at 48h and 6.8 oM at 72h treatment periods