OncoTargets and Therapy (Apr 2020)
Tripterine Restrains the Aggressiveness of Hepatocellular Carcinoma Cell via Regulating miRNA-532-5p/CXCL2 Axis
Abstract
Zhi Tao Jiang,1,* Yi Han,1,* Xiao Yan Liu,1 Ling Yan Lv,1 Jin Huo Pan,2 Chun Di Liu1 1Department of Pharmacy Office, Zhangjiagang Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, People’s Republic of China; 2College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jin Huo PanNanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of ChinaEmail [email protected] Di LiuZhangjiagang Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, People’s Republic of ChinaEmail [email protected]: Triterpene has attracted considerable interests because it exhibits anticancer effects. However, the effects of tripterine on hepatocellular carcinoma (HCC) are not well studied. In the current study, the mechanism of tripterine on HCC cells growth and metastasis was examined.Methods: The inhibitory effect on the growth and aggressiveness in HCC cells was analyzed by Cell Counting Kit-8 (CCK-8), wound healing and Transwell assay. The levels of microRNA-532-5p (miR-532-5p) in HCC cells and tissues were measured using qRT-PCR. The expression of chemokine (C-X-C Motif) ligand 2 (CXCL2) was determined by Western blotting and immunohistochemistry (IHC). Luciferase reporter gene assay was used to validate the binding between miR-532-5p and CXCL2. The impact of tripterine on the growth and metastasis of HCC cells in vivo was analyzed using transplanted tumor model and experimental lung metastasis model, respectively.Results: We found that tripterine inhibited HCC cells proliferation, migration ability and invasion. Under tripterine treatment, the level of miR-532-5p was strikingly raised, and overexpression of miR‑532-5p reduced cell viability and metastatic-related traits. In addition, we identified CXCL2 as a target of miR-532-5p in HCC. Rescue experiments indicated that overexpression of CXCL2 restored the migration and invasive capacity of HCC cells inhibited by miR-532-5p or tripterine treatment. Finally, the tumor growth and metastatic ability of HCC MHCC97H cell in vivo were also significantly restrained by tripterine. The expression of CXCL2 was distinctly decreased and miR-532-5p level was increased by tripterine in vivo.Conclusion: In conclusion, tripterine inhibits the growth, migration ability and invasiveness of HCC cells through intervening miR-532-5p/CXCL2.Keywords: tripterine, HCC, miRNA-532-5p, CXCL2, Metastasis
