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Fasudil inhibits proliferation and migration of Hep-2 laryngeal carcinoma cells

Authors Zhang X, Wu N

Received 28 July 2017

Accepted for publication 12 January 2018

Published 23 February 2018 Volume 2018:12 Pages 373—381

DOI https://doi.org/10.2147/DDDT.S147547

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Sukesh Voruganti


Xiaowen Zhang,1 Nan Wu2

1Medical Research Center, Shengjing Hospital of China Medical University, Shenyang, China; 2The Core Laboratory for Public Health Science and Practice, The First Affiliated Hospital of China Medical University, Shenyang, China

Background:
Rho-kinase signal pathway is a new target for cancer therapy. Fasudil, a selective Rho-kinase inhibitor, is found to exert antitumor effects on several types of cancer, but whether fasudil has antitumor effects on laryngeal carcinoma is still unknown. The aim of this study was to determine the effects of fasudil on laryngeal carcinoma and explore the underlying molecular mechanisms in this process.
Methods: After treatment with fasudil, changes in biological behaviors, including the growth, proliferation, clone formation, apoptosis, and migration of human laryngeal carcinoma cells (Hep-2 cells) were observed. The influences on apoptotic protease activity factor-1 (APAF-1)-mediated apoptosis pathway and the activities of matrix metalloproteinases (MMP-2 and MMP-9) were measured by Western blotting and gelatin zymography assay.
Results: Half-maximal inhibitory concentration of fasudil to Hep-2 cells was ~3.40×103 µM (95% CI: 2.53–4.66×103 µM). Moreover, fasudil treatment significantly decreased the ability of growth, proliferation, clone formation, and migration of Hep-2 cells, while remarkably increased the apoptosis rate. Furthermore, the expressions of APAF-1, caspase-9, and caspase-3 significantly increased in fasudil treatment group. Meanwhile, fasudil led to a remarkable decrease in the expressions and activities of MMP-2 and MMP-9.
Conclusion: Our findings first demonstrate that fasudil not only inhibits the proliferation of laryngeal carcinoma cells through activating APAF-1-mediated apoptosis pathway, but also prevents migration by inhibiting the activities of MMP-2 and MMP-9. Therefore, fasudil is an attractive antitumor drug candidate for the treatment of laryngeal carcinoma.

Keywords: fasudil, laryngeal carcinoma, apoptosis, apoptotic protease activity factor-1, matrix metalloproteinase

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