A selective cyclooxygenase-2 inhibitor suppresses the growth of endometriosis xenografts via antiangiogenic activity in severe combined immunodeficiency mice

Yuka Ozawa, Takashi Murakami, Mitsutoshi Tamura, Yukihiro Terada, Nobuo Yaegashi, Kunihiro Okamura

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)

Abstract

Objective: To investigate the effects of a selective cyclooxygenase (COX)-2 inhibitor on endometriosis xenografts in immunodeficient mice. Design: Prospective placebo-controlled study. Setting: An academic facility at a Japanese university graduate school of medicine. Patient(s): Eight human ovarian endometriomas from seven patients. Animal(s): Twenty-three female severe combined immunodeficiency (SCID) mice. Intervention(s): Human ovarian endometriomas were implanted into the peritonea of SCID mice. Vehicle alone or NS398 (a selective COX-2 inhibitor, 10 mg/kg of weight per day) were administered orally daily for 56 days after implantation. Mice were killed on the 56th day. Main Outcome Measure(s): Change in explants size and immunohistochemical analyses to evaluating the proliferation index, apoptosis index, microvessel density, and labeling index assessing vascular endothelial growth factor and COX-2 expression by the endometriotic lesion. Result(s): NS398 significantly decreased implant size in comparison to vehicle alone (NS398 [medians, with range in brackets]: 22.0% [19.0%-36.7%] vs. vehicle: 41.2% [31.0%-55.3%], P<.01). Microvessel density (85.3 per mm2 [53.9-157.0 per mm2] vs. 121.8 per mm2 [97.2-259.6 per mm2], P=.02) and the vascular endothelial growth factor (0.4 [0-1.1] vs. 0.6 [0.5-2.1], P=.03) and COX-2 (0.4 [0.4-0.5] vs. 0.6 [0.4-0.8], P=.03) labeling indices in stromal cells were significantly lower in the NS398 group than in the vehicle group. There were no differences in the proliferation or apoptosis indices between the two groups. Conclusion(s): Selective COX-2 inhibitors decreased the size of implants and effectively treated endometriosis.

Original languageEnglish
Pages (from-to)1146-1151
Number of pages6
JournalFertility and sterility
Volume86
Issue number4 SUPPL.
DOIs
Publication statusPublished - 2006 Oct

Keywords

  • Cox-2
  • Cyclooxygenase-2
  • endometriosis
  • selective cyclooxygenase-2 inhibitor
  • xenograft model

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynaecology

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