Synergistic effects of sorafenib and cilostazol in HepG2 cells

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Effat H.; Mohamed O.A.; Sharaky M.; Heikal S.; Elshahawy S.; Ayad E.G.

Journal: Journal of Biosciences

Publisher: Springer

Publication Date: 2026-07-16

Volume: 51   |   Issue: 3

Article No.: 35

ISSN: 2505991

DOI: 10.1007/s12038-026-00607-w

Scopus: View article on Scopus

Document Type: Article

Authors and Affiliations

Effat H., Medical Biochemistry and Molecular Biology Unit, Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo, 11796, Egypt; Mohamed O.A., Biochemistry and Molecular Biology Department, Theodor Bilharz Research Institute, Giza, 12411, Egypt; Sharaky M., Pharmacology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, 11796, Egypt; Heikal S., Chemistry Department, Faculty of Science, Helwan University, Cairo, 11795, Egypt; Elshahawy S., Chemistry Department, Faculty of Science, Helwan University, Cairo, 11795, Egypt; Ayad E.G., Chemistry Department, Faculty of Science, Helwan University, Cairo, 11795, Egypt

Abstract

Sorafenib, an established multi-kinase inhibitor, is a cornerstone of treatment for advanced hepatocellular carcinoma (HCC). This study explores the efficacy of combining sorafenib with cilostazol, a phosphodiesterase-3 inhibitor with emerging anticancer properties, using the HepG2 cell line. We assessed the effects on cell proliferation, apoptosis, and the expression levels of key regulatory proteins and genes, including VEGF, SMAD4, Bcl-2, TGF-β, Bax, and caspase-3. The combination treatment resulted in a significant reduction in the IC50 of sorafenib. Colony formation assays demonstrated that both cilostazol and sorafenib individually inhibited HepG2 cell growth, with combination therapy leading to a further decrease in colony numbers compared to individual treatments. Enhanced apoptosis was observed with the combination, as evidenced by increased Bax and caspase-3 levels and decreased Bcl-2 expression. Additionally, the combination therapy exhibited potent anti-angiogenic effects, significantly reducing VEGF and TGF-β levels. These findings suggest a synergistic interaction between sorafenib and cilostazol, offering promising insights for optimizing therapeutic strategies in HCC management. © The Author(s), under exclusive licence to Indian Academy of Sciences 2026.

Keywords

Angiogenesis; apoptosis; cilostazol; combination therapy; hepatocellular carcinoma; sorafenib; caspase 3; protein Bax; protein bcl 2; Smad4 protein; transforming growth factor beta; vasculotropin; bioassay; cell; disease treatment; gene expression; inhibitor; management; optimization; antiangiogenic activity; antineoplastic activity; Article; cancer chemotherapy; cell growth; cell proliferation; colony formation; comparative study; controlled study; drug efficacy; Hep-G2 cell line; human; IC50; liver cell carcinoma; protein expression; synergistic effect

Citation Information

Scopus Citations: 0

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