Expression of cyclooxygenase-2 in uterine endometrial cancer and anti-tumor effects of a selective COX-2 inhibitor

  • Authors:
    • Kiyoshi Hasegawa
    • Yoshimasa Ohashi
    • Kunimi Ishikawa
    • Akira Yasue
    • Rina Kato
    • Yumiko Achiwa
    • Eiji Nishio
    • Yasuhiro Udagawa
  • View Affiliations

  • Published online on: May 1, 2005     https://doi.org/10.3892/ijo.26.5.1419
  • Pages: 1419-1428
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Abstract

A role for cyclooxygenase-2 (COX-2) in the development and progression of various tumors has been identified. Selective COX-2 inhibitors produce anti-proliferative effects in various cancer cell lines that express COX-2. However, the mechanisms underlying anti-tumor effects are unclear. Furthermore, few studies have studied COX-2 expression in gynecological cancers, especially endometrial cancer. The current study had two goals. We investigated the correlation between COX-2 expression and clinicopathological factors of uterine endometrial cancer. We also investigated effects of treatment with etodolac, a selective COX-2 inhibitor, on the uterine endometrial cancer cell line TMG-L, which expresses COX-2. We conclusively confirmed expression of COX-2 mRNA and protein in endometrial cancer that exceeded levels of COX-2 seen in normal endometrium. However, no significant correlations were observed between COX-2 expression in endometrial cancer tumor samples and clinicopathological factors or disease-free survival rate of patients with endometrial cancer. Study of COX-2 inhibition of TMG-L cells showed that etodolac produced dose-dependent inhibition of cell proliferation through G1 phase cell-cycle arrest. Etodolac-induced cell-cycle arrest might be caused by increases in p53 and P21WAF1 protein expression. Production of basic-fibroblast growth factor (bFGF, a pro-angiogenesis factor) was inhibited by etodolac in a dose-dependent manner. Furthermore, telomerase activity was inhibited and expression of hTERT mRNA was significantly inhibited with etodolac, leading to the conclusion that anti-tumor effects of etodolac on TMG-L cells are due to inhibition of both angiogenesis and telomerase activity. These results strongly suggest that COX-2 inhibitors have potential as therapeutic (and possibly, chemopreventive) agents for endometrial cancers that overexpress COX-2.

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May 2005
Volume 26 Issue 5

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

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Spandidos Publications style
Hasegawa K, Ohashi Y, Ishikawa K, Yasue A, Kato R, Achiwa Y, Nishio E and Udagawa Y: Expression of cyclooxygenase-2 in uterine endometrial cancer and anti-tumor effects of a selective COX-2 inhibitor. Int J Oncol 26: 1419-1428, 2005
APA
Hasegawa, K., Ohashi, Y., Ishikawa, K., Yasue, A., Kato, R., Achiwa, Y. ... Udagawa, Y. (2005). Expression of cyclooxygenase-2 in uterine endometrial cancer and anti-tumor effects of a selective COX-2 inhibitor. International Journal of Oncology, 26, 1419-1428. https://doi.org/10.3892/ijo.26.5.1419
MLA
Hasegawa, K., Ohashi, Y., Ishikawa, K., Yasue, A., Kato, R., Achiwa, Y., Nishio, E., Udagawa, Y."Expression of cyclooxygenase-2 in uterine endometrial cancer and anti-tumor effects of a selective COX-2 inhibitor". International Journal of Oncology 26.5 (2005): 1419-1428.
Chicago
Hasegawa, K., Ohashi, Y., Ishikawa, K., Yasue, A., Kato, R., Achiwa, Y., Nishio, E., Udagawa, Y."Expression of cyclooxygenase-2 in uterine endometrial cancer and anti-tumor effects of a selective COX-2 inhibitor". International Journal of Oncology 26, no. 5 (2005): 1419-1428. https://doi.org/10.3892/ijo.26.5.1419