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Tanshinol inhibits the growth, migration and invasion of hepatocellular carcinoma cells via regulating the PI3K-AKT signaling pathway

Authors Zhu P, Liu Z, Zhou J, Chen Y

Received 31 August 2018

Accepted for publication 28 November 2018

Published 19 December 2018 Volume 2019:12 Pages 87—99

DOI https://doi.org/10.2147/OTT.S185997

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Dr Faris Farassati


Pingting Zhu,1,2,* Zhaoguo Liu,3,* JiaoJiao Zhou,1 Yuanyuan Chen1

1School of Nursing, Yangzhou University, Yangzhou, China; 2Jiangsu Key Laboratory of Zoonosis, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China; 3Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, China

*These authors contributed equally to this work

Background: Tanshinol is an active constituent of Salvia miltiorrhiza and possess anti-inflammatory, antioxidant, and anti-bacterial activity. Herein, we explored the role of tanshinol on the growth and aggressiveness of hepatocellular carcinoma (HCC) cells in vitro and in vivo.
Materials and methods: The proliferation of a panel of HCC cell lines was measured using MTT assay. The expressions of phosphatidylinositol 3 kinase (PI3K) and protein kinase B (AKT) were detected by immunofluorescence staining and immunohistochemical assay. The levels of Bcl-2 and Bax were determined using immunoblotting assay. The secretions of matrix metalloproteinase-2 (MMP-2) and MMP-9 were detected by ELISA. The migration and invasion abilities of HepG2 cell were determined using wound healing and Transwell invasion assays. The apoptosis of HepG2 cell induced by tanshinol was analyzed by Annexin V/propidium iodide staining. A xenograft model was constructed to investigate the inhibitory effect of tanshinol on HepG2 cell growth in vivo. To further investigate the role of tanshinol on the metastasis of HepG2 cell in vivo, an experimental metastasis assay was performed.
Results: Tanshinol inhibited the growth and colony formation of HCC cell in vitro. Tanshinol also induced the apoptosis of HepG2 cell and inhibited the migration and invasion of HepG2 cell. In in vivo experiments, tanshinol suppressed the tumor growth and metastasis of HepG2 cell. Furthermore, the phosphorylation of PI3K and AKT was decreased by tanshinol in vitro and in vivo.
Conclusion: Tanshinol exerts its anti-cancer effects via regulating the PI3K-AKT signaling pathway in HCC.

Keywords: tanshinol, HCC, migration, invasion, apoptosis

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