Expression of prostaglandin E2 receptors in oral squamous cell carcinomas and growth inhibitory effects of an EP3 selective antagonist, ONO-AE3-240

  • Authors:
    • Hiroshi Hoshikawa
    • Rieko Goto
    • Terushige Mori
    • Tomoo Mitani
    • Nozomu Mori
  • View Affiliations

  • Published online on: March 1, 2009     https://doi.org/10.3892/ijo_00000211
  • Pages: 847-852
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Abstract

Prostaglandin E2 (PGE2) can stimulate tumor progression by both direct and indirect mechanisms. However, its influence on cell proliferation is still unclear. The present study characterized expression of subtypes of PGE2 receptors in oral squamous cell carcinomas, while also investigating the effects of EP3 and EP4 selective antagonists on oral carcinoma cell lines. EP1, EP2, EP3 and EP4 receptor mRNAs were detected in 4, 5, 10 and 10 of 11 surgical specimens respectively. Application of an EP3 antagonist (ONO-AE3-240) strongly inhibited cell growth in COX-2 and PGE2 high expression cells (Ca9-22) but not in COX-2 and PGE2 low expression cells (HSC4). The antagonist also reduced the production of endogenous PGE2 and induced G0/G1 phase cell arrest. Addition of exogenous PGE2 only partly abrogated the growth inhibition, indicating that the anti-proliferative effect via EP3 receptor signaling was not only due to PGE2-dependent but also PGE2-independent mechanisms. In contrast, an EP4 antagonist (ONO-AE3-208) did not inhibit growth in either of the cancer cell lines. In summary, PGE2 receptor EP3 signaling probably contributes to development of oral carcinomas and use of EP3 antagonist may be a new therapeutic strategy for head and neck cancer.

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March 2009
Volume 34 Issue 3

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

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Spandidos Publications style
Hoshikawa H, Goto R, Mori T, Mitani T and Mori N: Expression of prostaglandin E2 receptors in oral squamous cell carcinomas and growth inhibitory effects of an EP3 selective antagonist, ONO-AE3-240. Int J Oncol 34: 847-852, 2009.
APA
Hoshikawa, H., Goto, R., Mori, T., Mitani, T., & Mori, N. (2009). Expression of prostaglandin E2 receptors in oral squamous cell carcinomas and growth inhibitory effects of an EP3 selective antagonist, ONO-AE3-240. International Journal of Oncology, 34, 847-852. https://doi.org/10.3892/ijo_00000211
MLA
Hoshikawa, H., Goto, R., Mori, T., Mitani, T., Mori, N."Expression of prostaglandin E2 receptors in oral squamous cell carcinomas and growth inhibitory effects of an EP3 selective antagonist, ONO-AE3-240". International Journal of Oncology 34.3 (2009): 847-852.
Chicago
Hoshikawa, H., Goto, R., Mori, T., Mitani, T., Mori, N."Expression of prostaglandin E2 receptors in oral squamous cell carcinomas and growth inhibitory effects of an EP3 selective antagonist, ONO-AE3-240". International Journal of Oncology 34, no. 3 (2009): 847-852. https://doi.org/10.3892/ijo_00000211