In silico and cheminformatics prediction with experimental validation of an adipogenesis cocktail, sorafenib with rosiglitazone for HCC dedifferentiation

Abstract

PURPOSE: Hepatocellular carcinoma (HCC) resistance to sorafenib treatment and other treatment strategies causes a higher mortality rate in patients diagnosed with HCC. RESEARCH QUESTION: HCC often develops resistance to sorafenib treatment and other therapies, leading to increased mortality rates in diagnosed patients. Herein, we propose a combined therapeutic approach using rosiglitazone, a key factor in cellular differentiation, along with adipogenesis inducers such as dexamethasone, IBMX, and insulin. Additionally, we included sorafenib, a primary drug for liver cancer treatment, in this combination cocktail and carried out the differentiation process in the presence of sorafenib. RESULTS: Our study demonstrates that this combination induces the formation of adipocytes from HCC cells over several days under specific conditions and steps. CONCLUSION: findings suggest that supplementing sorafenib with rosiglitazone and adipogenesis inducers may potentially transform HCC cells into adipocyte-like cells. Fat could be "the good" in the story of liver cancer alleviation, demonstrating the role of rosiglitazone.