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

Jr-DI Yang; Po-Fu Yueh; Tsai Lan Liao; Ying-Tzu Chen; Fei-Ting Hsu; I-Tsang Chiang; Ching Ming Chang; Wei-Shu Wang

doi:10.21873/anticanres.16636

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

Anticancer Res. 2023 Oct;43(10):4403-4412. doi: 10.21873/anticanres.16636.

Authors

Jr-DI Yang¹, Po-Fu Yueh², Tsai Lan Liao³, Ying-Tzu Chen³, Fei-Ting Hsu³, I-Tsang Chiang^#^{4

5

6

7}, Ching Ming Chang^#⁸, Wei-Shu Wang^#^{9

10}

Affiliations

¹ Division of Urology, Department of Surgery, National Yang-Ming Chiao Tung University Hospital, Yilan, Taiwan, R.O.C.
² Institute of Traditional Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan, R.O.C.
³ Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C.
⁴ Department of Radiation Oncology, Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.; john740604@yahoo.com.tw.
⁵ Department of Radiation Oncology, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.
⁶ Department of Medical Imaging and Radiologic Sciences, Central Taiwan University of Science and Technology, Taichung, Taiwan, R.O.C.
⁷ Medical Administrative Center, Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.
⁸ Department of Hematology and Medical Oncology, Show Chwan Memorial Hospital, Changhua, Taiwan, R.O.C.; mingogo@gmail.com.
⁹ Department of Medicine, National Yang Ming Chiao Tung University Hospital, Yilan County, Taiwan, R.O.C.; 11313@hosp.nycu.edu.tw.
¹⁰ School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, R.O.C.

^# Contributed equally.

PMID: 37772586
DOI: 10.21873/anticanres.16636

Abstract

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.

Keywords: 18β-glycyrrhetinic acid; Hepatocellular carcinoma; apoptosis; mTOR; regorafenib.