Suppression of the Development of Experimentally Induced Uterine Adenomyosis by a Novel Matrix Metalloproteinase Inhibitor, ONO-4817, in Mice

Takao Mori, Mori T, T Mori, S Yamasaki, Yamasaki S, Shin‐ichi Yamasaki, F Masui, Fujiko Masui, Masui F, Matsuda M, M Matsuda, Manabu Matsuda, Sasabe H, Haruko Sasabe, H Sasabe, Y F Zhou, Yingfang Zhou, Zhou YF
Experimental biology and medicine (Maywood, N.J.) · 2001 · vol. 226(5) , pp. 429–433 · doi:10.1177/153537020122600506 · PMID:11393170 · W2419339759
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A novel matrix metalloproteinase inhibitor, ONO-4817, suppressed the development, progression, and stromal cell invasion associated with experimentally induced uterine adenomyosis in mice.

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Abstract

The inhibitory effects of a novel, orally active matrix metalloproteinase (MMP) inhibitor, ONO-4817, on the development of uterine adenomyosis induced experimentally by pituitary grafting were examined in mice. Mice were given transplants of isologous anterior pituitary glands (PGs) into the right uterine lumen at 7 weeks of age and were fed chow containing 0.1% to 1.0% ONO-4817 from 8 to 14 weeks of age. Mice treated with 0.3% or 1.0% ONO-4817 showed a significantly lower incidence of the development of adenomyosis than vehicle-treated mice. To evaluate the inhibitory effects of ONO-4817 on the progression of the invasion of the adenomyotic tissues, mice receiving PG grafts at 7 weeks of age were treated with 1.0% ONO-4817 from 13 to 17 weeks of age. The degree of pathological progression of adenomyosis was graded from 1 to 5 in increments of 1. The degree of the progression of the lesion was less in the uteri exposed to ONO-4817 (2.71 +/- 0.93) than in the uteri not exposed to the inhibitor (4.33 +/- 0.75). Finally, the invasiveness of endometrial stromal cells obtained from adenomyotic uteri into Matrigel consisting mainly of type IV collagen and laminin was examined using an invasion assay. The assay showed that the treatment with ONO-4817 markedly suppressed the invasion of the stromal cells of the adenomyotic uteri into the gel. These results indicate that ONO-4817 may be an effective inhibitor of the development of adenomyosis.

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Condition tags

endometriosisadenomyosis

MeSH descriptors

Endometriosis Matrix Metalloproteinase Inhibitors Phenyl Ethers Protease Inhibitors Uterine Diseases Animals Endometriosis Endometriosis Endometriosis Endometriosis Female Mice Mice, Inbred Strains Phenyl Ethers Pituitary Gland Pituitary Gland Protease Inhibitors Transplantation, Isogeneic Uterine Diseases Uterine Diseases

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