Anti-gallbladder cancer activities and toxicity studies of glycyrrhetinic acid derivative as a novel PPARγagonist

Haizhang Ma¹Gaozhong Xiong²Mei Qi¹Yuan Xia²Yunxue Zhao²Chunyan Ji²Juan Sun³Tao Sun¹Min Liu^4*

• ¹Qilu Hospital of Shandong University, Jinan, China
• ²Shandong University Cheeloo College of Medicine, Jinan, China
• ³Zhejiang University of Science and Technology, Hangzhou, China
• ⁴Department of International Medicine, Qilu Hospital of Shandong University, Jinan, China

The PPARγ agonist serves as a clinical drug for dyslipidemias and diabetes. Ongoing studies indicate its antiproliferative and tumoricidal properties, positioning PPARγ agonists as promising therapeutic targets for cancer. This study delves into the in vitro and in vivo anticancer efficacy of a novel PPARγ agonist, the glycyrrhetinic acid derivative 4c (PG-4c), in gallbladder cancer. PG-4c demonstrated superior anticancer activity in GBC-SD cells compared to the conventional chemotherapy gemcitabine. The efficacy of PG-4c extends to in vivo models, showing a significant inhibitory effect on tumor growth in zebrafish models transplanted with human GBC-SD cells and tumor-bearing nude mice. Notably, PG-4c exhibited lower toxicity than the traditional PPARγ agonist, pioglitazone, as evidenced by in vivo animal toxicity assays. In summary, our findings suggest that PG-4c holds considerable promise as an effective chemotherapy agent for gallbladder cancer.