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Synergistic antitumor effects of tanshinone IIA and sorafenib or its derivative SC-1 in hepatocellular carcinoma cells

Authors Chiu CM, Huang SY, Chang SF, Liao KF, Chiu SC

Received 4 January 2018

Accepted for publication 22 February 2018

Published 29 March 2018 Volume 2018:11 Pages 1777—1785

DOI https://doi.org/10.2147/OTT.S161534

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Ingrid Espinoza


Chien-Ming Chiu,1 Sung-Ying Huang,2 Shu-Fang Chang,3 Kuan-Fu Liao,4,5 Sheng-Chun Chiu3,6,7

1Division of Colorectal Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan; 2Department of Ophthalmology, Hsinchu Mackay Memorial Hospital, Hsinchu, Taiwan; 3Department of Research, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan; 4Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan; 5Department of Internal Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan; 6Department of Laboratory Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan; 7General Education Center, Tzu Chi University of Science and Technology, Hualien, Taiwan

Introduction:
Hepatocellular carcinoma (HCC) is the most common form of hepatic malignancy in the world. We aimed to determine the effect of tanshinone IIA (Tan-IIA) in combination with sorafenib or its derivative SC-1 on cytotoxicity, apoptosis, and metastasis in human HCC cells.
Materials and methods: Cytotoxicity was detected by MTT assay. Apoptosis and sub-G1 populations were analyzed by flow cytometry. Cell migration and invasion were evaluated by Transwell assay. Protein expression was detected by Western blot.
Results:
Tan-IIA combined with sorafenib or SC-1 exerted synergistic cytotoxicity in HCC cells. Elevated proportions of sub-G1 and caspase activation were observed in the combinative treatments; in addition, marked inhibition of cell migration and invasion, which could be mediated by the modulation of epithelial–mesenchymal transition was observed. pSTAT3 levels were significantly reduced as well.
Conclusion: A combination therapy using Tan-IIA and sorafenib or SC-1 could be a promising approach to target HCC, and further preclinical investigations are warranted to establish their synergetic advantage.

Keywords: tanshinone IIA, hepatocellular carcinoma, sorafenib, SC-1, STAT3, metastasis, combination therapy

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