Effect of inhibition of the ROCK isoform on RT2 malignant glioma cells

Anticancer Res. 2010 Sep;30(9):3509-14.

Abstract

Background: Malignant glioma is one of the most intractable diseases in the human body. Rho-kinase (ROCK) is overexpressed and has been proposed as the main cause for the refractoriness of the disease. Since efficacious treatment is required, this study investigated the effect of inhibition of ROCK isoforms.

Materials and methods: The short hairpin RNA transcription vector was transfected into the RT2 rat glioma cell line and the characteristics of the cells were investigated. The effect of nimustine hydrochloride (ACNU) anti-neoplastic agent on cells was also measured.

Results: Inhibition of ROCK isoforms did not alter cell growth. Cell cycle analysis revealed that ROCK1 down-regulation reduced the G(0) phase population and ROCK2 down-regulation reduced the G(2)/M phase population. When ROCK1-down-regulated cells were exposed to ACNU, they demonstrated susceptibility to the agent.

Conclusion: The roles of ROCK1 and ROCK2 may be different in glioma cells. Furthermore, the combination of ROCK1 down-regulation and an anti-neoplastic agent may be useful for the therapy of malignant glioma.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Knockdown Techniques
  • Glioma / genetics
  • Glioma / metabolism*
  • Humans
  • Immunoblotting
  • Isoenzymes
  • Nimustine / pharmacology
  • RNA, Small Interfering
  • Rats
  • Transfection
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism*

Substances

  • Antineoplastic Agents
  • Isoenzymes
  • RNA, Small Interfering
  • Nimustine
  • rho-Associated Kinases