Antitumor effects of inhibitors of nitric oxide synthase or cyclooxygenase-2 on human KB carcinoma cells overexpressing COX-2

  • Authors:
    • Nao Ohtsu
    • Kazuki Takaoka
    • Emi Segawa
    • Susumu Hashitani
    • Kazuma Noguchi
    • Hiromitsu Kishimoto
    • Masahiro Urade
  • View Affiliations

  • Published online on: July 1, 2010     https://doi.org/10.3892/or_00000825
  • Pages: 31-36
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Abstract

Inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 are major inflammatory mediators. Nitric oxide (NO) produced by iNOS has been shown to have an important role in carcinogenesis. Recent studies have suggested that COX-2 expression also contributes to carcinogenesis, as well as tumor growth, invasion, and metastasis. COX-2 inhibitors such as celecoxib are widely recognized to have antitumor activity, but can cause adverse effects. We investigated possible relations between COX-2 and NO with the use of a human epidermoid carcinoma cell line, designated KB, in which overexpression of COX-2 protein was induced by gene transfer. We also assessed the possibility of using NOS inhibitor as an antitumor drug. We isolated a COX-2 transfected clone (KB/COX-2) and used a neomycin-transfected clone (KB/neo) as control. NG-nitro-L-arginine-methyl ester (L-NAME) was used as a NOS inhibitor, dihydrochloride (1400W) as an iNOS inhibitor, and celecoxib as a selective COX-2 inhibitor. All agents inhibited the cell growth of both clones to similar extents in a dose-dependent manner. Prostaglandin E2 (PGE2) production and COX-2 expression in KB/COX-2 were inhibited not only by celecoxib, but also by L-NAME and 1400W. The decreases in PGE2 production and COX-2 expression were most prominent with celecoxib and L-NAME. In vivo, L-NAME and celecoxib significantly inhibited the proliferation of KB/COX-2-xenografted tumors. Tumor weight was reduced by L-NAME (60.6% decrease), 1400W (38.0% decrease), and celecoxib (74.5% decrease) as compared with the control after 21 days of treatment. Immunohistochemically, xenografted tumors expressed COX-2, iNOS, and eNOS. Such expression was suppressed by treatment with L-NAME and celecoxib. These results suggest that L-NAME and celecoxib significantly inhibit the proliferation of murine squamous cell carcinoma in vivo. L-NAME as well as celecoxib might thus be useful for the design and development of new antitumor drugs.

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July 2010
Volume 24 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Ohtsu N, Takaoka K, Segawa E, Hashitani S, Noguchi K, Kishimoto H and Urade M: Antitumor effects of inhibitors of nitric oxide synthase or cyclooxygenase-2 on human KB carcinoma cells overexpressing COX-2 . Oncol Rep 24: 31-36, 2010.
APA
Ohtsu, N., Takaoka, K., Segawa, E., Hashitani, S., Noguchi, K., Kishimoto, H., & Urade, M. (2010). Antitumor effects of inhibitors of nitric oxide synthase or cyclooxygenase-2 on human KB carcinoma cells overexpressing COX-2 . Oncology Reports, 24, 31-36. https://doi.org/10.3892/or_00000825
MLA
Ohtsu, N., Takaoka, K., Segawa, E., Hashitani, S., Noguchi, K., Kishimoto, H., Urade, M."Antitumor effects of inhibitors of nitric oxide synthase or cyclooxygenase-2 on human KB carcinoma cells overexpressing COX-2 ". Oncology Reports 24.1 (2010): 31-36.
Chicago
Ohtsu, N., Takaoka, K., Segawa, E., Hashitani, S., Noguchi, K., Kishimoto, H., Urade, M."Antitumor effects of inhibitors of nitric oxide synthase or cyclooxygenase-2 on human KB carcinoma cells overexpressing COX-2 ". Oncology Reports 24, no. 1 (2010): 31-36. https://doi.org/10.3892/or_00000825