Abstract
Monoclonal antibodies, such as bevacizumab and cetuximab, have revolutionized targeted immunotherapy and have shown promising results in treating lung and hepatocellular carcinoma. However, a range of side effects are observed, urging the development of approaches to minimize mAb’s side effects while preserving their efficacy. Melittin, the main constituent of BV, has been recently proposed as a promising natural product for combination with immunotherapy to reduce the effective dose used. Here, we studied the impact of combining melittin with bevacizumab and cetuximab on lowering the therapeutic doses of these mAbs. We measured the effects of bevacizumab and cetuximab alone or in combination with melittin on lung and hepatocellular carcinoma cell lines (A549 and HepG2, respectively). Our results revealed enhanced cytotoxicity of bevacizumab and cetuximab in both the A549 and HepG2 cancer cell lines when either agent was combined with melittin, as calculated by the combination index from the MTT assay. These results were confirmed via histopathological examination and apoptosis analysis via flow cytometry. Mechanistically, RT‒qPCR revealed that this synergism was associated with significant changes in the gene expression of CASPASE3, Bcl2, VEGFR2, and EGFR. Our findings suggest combining melittin with bevacizumab and cetuximab enhances their effectiveness against carcinoma cell lines.