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
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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