Enhancement of cisplatin-induced cytotoxicity by ROCK inhibitor through suppression of focal adhesion kinase-independent mechanism in lung carcinoma cells

  • Authors:
    • Tadashi Igishi
    • Masaaki Mikami
    • Kaori Murakami
    • Shingo Matsumoto
    • Yasushi Shigeoka
    • Hirofumi Nakanishi
    • Kazuhito Yasuda
    • J. Silvio Gutkind
    • Yutaka Hitsuda
    • Eiji Shimizu
  • View Affiliations

  • Published online on: October 1, 2003     https://doi.org/10.3892/ijo.23.4.1079
  • Pages: 1079-1085
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Abstract

Intracellular signaling through Rho-associated coiled-coil forming kinase (ROCK) is a target of antimetastatic therapy and is proposed to be involved in carcinogenesis. Focal adhesion kinase (FAK) functions downstream of ROCK and participates in anti-apoptotic signaling. We hypothesized that a specific ROCK inhibitor, Y-27632, may exert a pro-apoptotic effect in combination with anticancer agents through the suppression of FAK. A549 lung carcinoma cells were treated with Y-27632 and cisplatin. The simultaneous combination did not exert any additional effect, whereas sequential treatment, in which cisplatin followed Y-27632, enhanced cytotoxicity in concentration- and time-dependent manner. Y-27632 did not suppress tyrosine phosphorylation of FAK in A549-FAK, the active form of FAK expressing A549 cells, as observed in parental cells. Nevertheless, the pretreatment of A549-FAK cells with Y-27632 still enhanced cisplatin-induced cytotoxicity. It was concluded that the ROCK inhibitor enhances cisplatin-induced cytotoxicity through FAK suppression-independent mechanism(s). These observations raise the possibility that the inhibition of the ROCK-mediated signal enhances the effect of anti-cancer agents in addition to its antimetastatic property.

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October 2003
Volume 23 Issue 4

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

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Spandidos Publications style
Igishi T, Mikami M, Murakami K, Matsumoto S, Shigeoka Y, Nakanishi H, Yasuda K, Gutkind JS, Hitsuda Y, Shimizu E, Shimizu E, et al: Enhancement of cisplatin-induced cytotoxicity by ROCK inhibitor through suppression of focal adhesion kinase-independent mechanism in lung carcinoma cells. Int J Oncol 23: 1079-1085, 2003
APA
Igishi, T., Mikami, M., Murakami, K., Matsumoto, S., Shigeoka, Y., Nakanishi, H. ... Shimizu, E. (2003). Enhancement of cisplatin-induced cytotoxicity by ROCK inhibitor through suppression of focal adhesion kinase-independent mechanism in lung carcinoma cells. International Journal of Oncology, 23, 1079-1085. https://doi.org/10.3892/ijo.23.4.1079
MLA
Igishi, T., Mikami, M., Murakami, K., Matsumoto, S., Shigeoka, Y., Nakanishi, H., Yasuda, K., Gutkind, J. S., Hitsuda, Y., Shimizu, E."Enhancement of cisplatin-induced cytotoxicity by ROCK inhibitor through suppression of focal adhesion kinase-independent mechanism in lung carcinoma cells". International Journal of Oncology 23.4 (2003): 1079-1085.
Chicago
Igishi, T., Mikami, M., Murakami, K., Matsumoto, S., Shigeoka, Y., Nakanishi, H., Yasuda, K., Gutkind, J. S., Hitsuda, Y., Shimizu, E."Enhancement of cisplatin-induced cytotoxicity by ROCK inhibitor through suppression of focal adhesion kinase-independent mechanism in lung carcinoma cells". International Journal of Oncology 23, no. 4 (2003): 1079-1085. https://doi.org/10.3892/ijo.23.4.1079