Fasudil inhibits prostate cancer-induced angiogenesis in vitro

Chen,Weihua; Mao,Kaili; Hua-Huy,Thong; Bei,Yihua; Liu,Zhongmin; Dinh-Xuan,Anh-Tuan

doi:10.3892/or.2014.3491

Fasudil inhibits prostate cancer-induced angiogenesis in vitro

Authors:
- Weihua Chen
- Kaili Mao
- Thong Hua-Huy
- Yihua Bei
- Zhongmin Liu
- Anh-Tuan Dinh-Xuan
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Affiliations: Medical School, Service de Physiologie, Paris Descartes University, EA 2511, Hôpital Cochin, 75014 Paris, France, Department of Urology, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai 200120, P.R. China, Clinical and Translational Research Center, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai 200120, P.R. China
Published online on: September 17, 2014 https://doi.org/10.3892/or.2014.3491
Pages: 2795-2802

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Abstract

Inhibition of angiogenesis is an important therapeutic strategy for advanced stage prostate cancer (PCa). RhoA/Rho-associated protein kinases (ROCK) are key regulators of the cytoskeleton and have been implicated in PCa angiogenesis. We investigated the anti-angiogenic effects of fasudil, a ROCK inhibitor, on PCa-induced angiogenesis in vitro. Proliferation of PCa-conditioned human umbilical vein endothelial cells (HUVECs) was assessed using a bromodeoxyuridine (BrdU) assay, and migration was assessed with a wound healing assay. In vitro angiogenesis of PCa-conditioned HUVECs was evaluated by tube formation and a spheroid sprouting assay. Fasudil inhibited PCa-induced endothelial cell proliferation at a concentration of 100 µM, and also decreased PCa-induced endothelial cell migration at a concentration of 30 µM. In the in vitro angiogenesis assay, fasudil exerted a more significant effect. Tube formation was significantly inhibited at fasudil concentrations exceeding 3 µM, and spheroid sprouts were significantly thinner and shorter (at fasudil concentrations of 10 and 30 µM, respectively). Western blotting results showed that expression of phosphorylated myosin phosphatase target subunit 1 (MYPT-1) was significantly lower after fasudil treatment, confirming that fasudil inhibited ROCK activity in these model systems. These data suggest that fasudil may be a useful anti-angiogenic agent for PCa.

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