LAUSR

Aim: The present study is focusing on using sorafenib, rosiglitazone, and adipogenesis-inducers cocktail (Insulin, Dexamethasone and IBMX) as a combination treatment to induce hepatocellular carcinoma (HCC) cell lines differentiation into adipocyte functioning cells, a strategy for effecting examined cancer cell lines to lose carcinogenicity properties and hopefully, turning into near-normal cells, with near-normal activity. The liver is one of the most vital organs in the body, any malfunctioning in the liver affects the whole body's health and performance. By 2040, 1.4 million people could be diagnosed with liver cancer and 1.3 million people could die from the disease, thus, trying an attempt to stop or reverse this cancer, would be a great break-through. Materials, Methods and Results: Using the current differentiation-induction cocktail to turn HepG2 and Hep3B HCC cancer cells into adipocytes, was confirmed by Oil Red O staining and morphological changes, and significantly expressed "adiponectin" level. Moreover, the cellular molecular markers p53, PPAR-γ, E-cadherin/β-catenin complex, and caspase-3 activities were significantly enhanced in the cocktail induced-differentiated cells, confirming the effectiveness of the proposed cocktail for ameliorating STAT3 together with inducing apoptosis (clonogenicity) , in comparison to control cells or HCC cells treated with the cocktail individual drugs. The differentiation-induction cocktail through rosiglitazone activated PPAR-γ which in turn increased HCC cells sensitivity to insulin to induce lipid uptake. Sorafenib, in the cocktail, role to block tumor cell proliferation via inhibiting STAT3 signaling pathway activation. In conclusion, the current proposed differentiation-induction cocktail after further in vivo confirmation (future prospective) might open a different avenue for liver cancer treatment. Citation Format: Aya Anis, Ahmed M. Mostafa, Nadia M. Hamdy, Ahmed S. Sultan. The promising recipe sorafenib rosiglitazone and adipogenesis inducers cocktail for in vitro hepatocellular carcinoma differentiation induction besiege carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1596.