A selective cyclooxygenase-2 inhibitor suppresses the growth of endometriosis xenografts via antiangiogenic activity in severe combined immunodeficiency mice.
OBJECTIVE
To investigate the effects of a selective cyclooxygenase (COX)-2 inhibitor on endometriosis xenografts in immunodeficient mice.


METHODS
Prospective placebo-controlled study.


METHODS
An academic facility at a Japanese university graduate school of medicine.


METHODS
Eight human ovarian endometriomas from seven patients.


METHODS
Twenty-three female severe combined immunodeficiency (SCID) mice.


METHODS
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Selective COX-2 inhibitors decreased the size of implants and effectively treated endometriosis.
Ozawa
Yuka
Y
Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Murakami
Takashi
T
Tamura
Mitsutoshi
M
Terada
Yukihiro
Y
Yaegashi
Nobuo
N
Okamura
Kunihiro
K
D000328:Adult; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D001808:Blood Vessels / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004715:Endometriosis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007158:Immunologic Techniques; D051379:Mice; D016513:Mice, SCID; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000503:physiopathology*; D009578:Nitrobenzenes / Q000494:pharmacology*; D010537:Peritoneum / Q000601:surgery; D013194:Staining and Labeling; D013449:Sulfonamides / Q000494:pharmacology*; D014183:Transplantation, Heterologous
D020533:Angiogenesis Inhibitors; D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide