Pharmacological inhibition of Rho-kinase (ROCK) signaling enhances cisplatin resistance in neuroblastoma cells

  • Authors:
    • Catharine A. Street
    • Alissa A. Routhier
    • Carrie Spencer
    • Ashley L. Perkins
    • Katherine Masterjohn
    • Alexander Hackathorn
    • John Montalvo
    • Emily A. Dennstedt
    • Brad A. Bryan
  • Corresponding author:
  • View Affiliations

  • Published online on: Monday, November 1, 2010
  • Pages: 1297-1305
  • DOI: 10.3892/ijo_00000781

Abstract

The role of the RhoA/Rho kinase (ROCK) signaling pathway in cell survival remains a very controversial issue, with its activation being pro-apoptotic in many cell types and anti-apoptotic in others. To test if ROCK inhibition contributes to tumor cell survival or death following chemotherapy, we treated cisplatin damaged neuroblastoma cells with a pharmacological ROCK inhibitor (Y27632) or sham, and monitored cell survival, accumulation of a chemoresistant phenotype, and in vivo tumor formation. Additionally, we assayed if ROCK inhibition altered the expression of genes known to be involved in cisplatin resistance. Our studies indicate that ROCK inhibition results in increased cell survival, acquired chemoresistance, and enhanced tumor survival following cisplatin cytotoxicity, due in part to altered expression of cisplatin resistance genes. These findings suggest that ROCK inhibition in combination with cisplatin chemotherapy may lead to enhanced tumor chemoresistance in neuroblastoma.
Journal Cover

November 2010
Volume 37 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
(total number of cites)

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APA
Street, C.A., Routhier, A.A., Spencer, C., Perkins, A.L., Masterjohn, K., Hackathorn, A. ... Bryan, B.A. (2010). Pharmacological inhibition of Rho-kinase (ROCK) signaling enhances cisplatin resistance in neuroblastoma cells. International Journal of Oncology, 37, 1297-1305. http://dx.doi.org/10.3892/ijo_00000781
MLA
Street, C. A., Routhier, A. A., Spencer, C., Perkins, A. L., Masterjohn, K., Hackathorn, A., Montalvo, J., Dennstedt, E. A., Bryan, B. A."Pharmacological inhibition of Rho-kinase (ROCK) signaling enhances cisplatin resistance in neuroblastoma cells". International Journal of Oncology 37.5 (2010): 1297-1305.
Chicago
Street, C. A., Routhier, A. A., Spencer, C., Perkins, A. L., Masterjohn, K., Hackathorn, A., Montalvo, J., Dennstedt, E. A., Bryan, B. A."Pharmacological inhibition of Rho-kinase (ROCK) signaling enhances cisplatin resistance in neuroblastoma cells". International Journal of Oncology 37, no. 5 (2010): 1297-1305. http://dx.doi.org/10.3892/ijo_00000781