2006 Fiscal Year Final Research Report Summary
A selective cyclooxygenase-2 inhibitor suppresses the growth of endometriosis xenografts via antiangiogenic activity in severe combined immunodeficiency mice.
| Project/Area Number |
17591712
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
TAMURA Mitsutoshi Tohoku University, Hospital, Assistant Professor, 病院, 助手 (90292325)
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Takashi Tohoku University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (20240666)
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| Project Period (FY) |
2005 – 2006
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| Keywords | COX-2 / endometriosis |
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| Research Abstract |
Objective : To investigate the effects of a selective COX-2 inhibitor on endometriosis xenografts in immunodeficient mice.
Design : Prospective placebo-controlled study.
Animals : Twenty-three female SCID mice.
Patients : Eight human ovarian endometriomas from seven patients.
Interventions : Human ovarian endometriomas were implanted into the peritonea of SCID mice. NS-398 (a selective COX-2 inhibitor, 10 mg/kg wt/day) or vehicle alone were orally administered daily for 56 days. Mice were sacrificed on the 56th day. Main Outcome Measures : Change in explants size, and immunohistochemical analysis to evaluate the proliferation index, apoptosis index, microvessel density, and labeling index assessing VEGF and COX-2 expression by the endometriosis lesion. Results : Treatment with NS-398 significantly decreased implant size in comparison with vehicle alone (NS-398 : 25.9% ± 5.7 vs. vehicle : 42.4% ± 9.2, p<0.01). Microvessel density (NS-398 : 89.5/cm^2± 30.8 vs. vehicle : 134.2/cm±52.3, p=0.02) and the VEGF labeling (NS-398 : 0.4 ± 0.3 vs. vehicle 0.8 ± 0.3, p=0.03) and COX-2 labeling (NS-398 : 0.4 ± 0.1 vs. vehicle 0.6 ±0.1, p=0.03) indices were significantly lower in the NS-398 group than in the vehicle group. There were no differences in the proliferation and apoptosis indices between the two groups.
Conclusions : Selective COX-2 inhibitors downregulate VEGF, resulting in decreased angiogenesis and the effective treatment of endometriosis.
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