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Reproductive Sciences, Vol. 14, No. 8 suppl, 20-27 (2007)
DOI: 10.1177/1933719107311464

Comparative Effects of SPRM Asoprisnil (J867) on Proliferation, Apoptosis, and the Expression of Growth Factors in Cultured Uterine Leiomyoma Cells and Normal Myometrial Cells

Noriyuki Ohara, MD, PhD

Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan

Akira Morikawa, MD

Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan

Wei Chen, MD, PhD

Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan

Jiayin Wang, MD, PhD

Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan

Deborah A. DeManno, PhD

TAP Pharmaceutical Products Inc, Lake Forest, Illinois

Kristof Chwalisz, MD, PhD

TAP Pharmaceutical Products Inc, Lake Forest, Illinois

Takeshi Maruo, MD, PhD

Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan, maruo{at}kobe-u.ac.jp

Progesterone plays a pivotal role in controlling uterine leiomyoma growth. The authors review studies they conducted to evaluate the comparative effects of asoprisnil on proliferation, apoptosis, and growth factor expression in cultured leiomyoma and normal myometrial cells. Treatment with asoprisnil decreased the proliferating cell nuclear antigen—positive rate and the number of viable cells and increased the terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling— positive rate in cultured leiomyoma cells in a dose-dependent manner ( P < .05). Similarly, asoprisnil decreased Bcl-2 expression and increased cleaved caspase-3 and cleaved poly(adenosine 5'-diphosphate-ribose) polymerase in leiomyoma cells but not in normal myometrial cells. Similarly, asoprisnil decreased epidermal growth factor (EGF), insulin-like growth factor—I (IGF-I), and transforming growth factor (TGF) β mRNA and protein expression, as well as EGF receptor, IGF-IR{alpha}, and TGF RII protein expression in leiomyoma cells but not in cultured normal myometrial cells. These results suggest that asoprisnil selectively inhibits proliferation by downregulating the growth factors and their receptor expression and induces apoptosis in leiomyoma cells without affecting proliferation and apoptosis in normal myometrial cells.

Key Words: Leiomyomata • selective progesterone receptor modulator • asoprisnil • proliferation • apoptosis.


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