Unlocking Synergistic Potential: Enhancing Regorafenib Efficacy in Hepatocellular Carcinoma Through Combination Therapy With 18β-Glycyrrhetinic Acid

BACKGROUND/AIM: Hepatocellular carcinoma (HCC) is a primary liver cancer with limited treatment options and poor prognosis. Regorafenib, a multi-kinase inhibitor, has shown promise in HCC treatment; however, its efficacy can be enhanced by combining it with other agents. 18β-glycyrrhetinic acid (18β-gly) is a natural compound with potential anti-cancer properties. MATERIALS AND METHODS: The toxicity and mechanism of regorafenib and 18β-gly was assessed on Hep3B cells, Huh7 cells, and Hep3B bearing animal model. RESULTS: The combination of regorafenib and 18β-gly exhibited synergistic toxicity in HCC cells and animal model. Importantly, no significant differences in body weight or major tissue damage were observed after treatment with the combination of two drugs. Furthermore, the combination treatment modulated apoptosis-related markers and the mTOR signaling pathway. CONCLUSION: The study provides evidence for the synergistic effect of 18β-gly and regorafenib in a HCC model. The combination treatment modulated apoptosis-related markers and the mTOR signaling pathway, highlighting potential mechanisms underlying its therapeutic efficacy.