Article Text

Download PDFPDF
Fasudil Inhibits Lysophosphatidic Acid-Induced Invasiveness of Human Ovarian Cancer Cells
  1. Seiji Ogata, MD*,
  2. Ken-Ichirou Morishige, MD, PhD*,
  3. Kenjiro Sawada, MD, PhD*,
  4. Kae Hashimoto, MD, PhD,
  5. Seiji Mabuchi, MD, PhD*,
  6. Chiaki Kawase, MD*,
  7. Chifumi Ooyagi, MD*,
  8. Masahiro Sakata, MD, PhD* and
  9. Tadashi Kimura, MD, PhD*
  1. * Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan; and
  2. Molecular and Cellular Biology Research, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
  1. Address correspondence and reprint requests to Ken-ichirou Morishige, MD, PhD, Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan. E-mail: mken{at}


Ovarian cancer is known to be highly invasive. The poor prognosis of advanced ovarian cancer comes from increased invasiveness of human ovarian cancer cells. The lysophosphatidic acid (LPA)/Rho/Rho-associated kinase (ROCK) pathway is intimately involved in the course of ovarian cancer progression, and the inhibition of this pathway attenuates ovarian cancer invasiveness. Fasudil (1-[5-isoquinolinesulfonyl]-homopiperazine; HA-1077) is a drug that has been in clinical use in Japan for the prevention of vasospasm after subarachnoid hemorrhage and is known to be a potent ROCK-specific inhibitor. In this study, we examined the effect of fasudil on LPA-induced invasiveness of human ovarian cancer cells to explore the potential of fasudil as an anticancer agent against ovarian cancer. Fasudil induced changes in cell morphology but not in cell viability. Fasudil significantly inhibited LPA-induced invasion and motility of human ovarian cancer cells in a dose-dependent manner. Furthermore, fasudil caused the loss of intracellular cytoskeletal rearrangement, which is necessary for cell motility, such as stress fiber formation and focal adhesion assembly. Fasudil suppressed LPA-induced tyrosine phosphorylation of paxillin, a representative focal adhesion protein, and serine phosphorylation of myosin light chain, which are essential for the process for cell migration. These findings showed that fasudil attenuated the invasiveness of human ovarian cancer cells via inhibition of the LPA/Rho/ROCK pathway. In SKOV-3ip1 ovarian cancer xenografts, intraperitoneal treatment with fasudil significantly reduced tumor burden and ascites formation. Our findings suggest that fasudil might be useful to prevent the progression of ovarian cancer in clinical settings.

  • Fasudil
  • Rho-associated kinase
  • Lysophosphatidic acid
  • Cancer invasion
  • Ovarian cancer

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.