18[Formula: see text]-Glycyrrhetinic Acid Inhibits TGF-[Formula: see text]-Induced Epithelial-to-Mesenchymal Transition and Metastasis of Hepatocellular Carcinoma by Targeting STAT3.

Abstract

18[Formula: see text]-glycyrrhetinic acid (GA) is the active ingredient of the traditional Chinese medicinal herb Glycyrrhizae radix et rhizoma. We previously demonstrated that GA inhibited tumor growth in hepatocellular carcinoma (HCC). However, the effect of GA on transforming growth factor-[Formula: see text] (TGF-[Formula: see text]-induced epithelial-mesenchymal transition (EMT) and metastasis were still unclear. In this study, in vitro transwell assays and immunofluorescence (IF) demonstrated that GA inhibited TGF-[Formula: see text]-induced migration, invasion and EMT of HCC cells. However, it had little effect on the inhibition of proliferation by TGF-[Formula: see text]. Moreover, we confirmed that GA suppressed the metastasis of HCC cells in vivousing an ectopic lung metastasis model. Furthermore, we found that GA inhibited TGF-[Formula: see text]-induced EMT mainly by reducing the phosphorylation of signal transducer and activator of transcription 3 (STAT3), which played an essential role in TGF-[Formula: see text]-induced EMT and cell mobility. Mechanistically, GA inhibited the phosphorylation of STAT3 by increasing the expression of Src homology 2 domain-containing protein tyrosine phosphatases 1 and 2 (SHP1 and SHP2). Therefore, we concluded that GA inhibited TGF-[Formula: see text]-induced EMT and metastasis via the SHP1&SHP2/STAT3/Snail pathway. Our data provide an attractive therapeutic target for future multimodal management of HCC.

• Authors: Mo Jie, Zhao-Qi Zhang, Ning Deng, Qiu-Meng Liu, Chao Wang, Qian-Yun Ge, Peng-Chen Du, Sha-Sha Song, Xue-Wu Zhang, Long-Xin, Hui-Fang Liang, Liang Chu, Lei Zhang, Xiao-Ping Chen, Jin Chen, Han-Hua Dong, Bi-Xiang Zhang
• Journal: The American journal of Chinese medicine (Am J Chin Med) Vol. 50 Issue 1 Pg. 313-332 ( 2022) ISSN: 1793-6853 [Electronic] Singapore
• PMID: 34963428 (Publication Type: Journal Article)

Chemical References

• STAT3 Transcription Factor
• STAT3 protein, human
• Transforming Growth Factor beta1
• Glycyrrhetinic Acid

Topics

• Carcinoma, Hepatocellular (drug therapy, genetics, metabolism)
• Cell Line, Tumor
• Cell Movement
• Epithelial-Mesenchymal Transition
• Glycyrrhetinic Acid (pharmacology)
• Humans
• Liver Neoplasms (pathology)
• Neoplasm Invasiveness
• STAT3 Transcription Factor (metabolism)
• Transforming Growth Factor beta1 (genetics, metabolism)