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

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Abstract

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-IRα, 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.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-Cho, Chuo-Ku, Kobe, 650-0017, Japan

    Noriyuki Ohara MD, PhD, Akira Morikawa MD, Wei Chen MD, PhD, Jiayin Wang MD, PhD & Takeshi Maruo MD, PhD

  2. TAP Pharmaceutical Products Inc, Lake Forest, Illinois, USA

    Deborah A. DeManno PhD & Kristof Chwalisz MD, PhD

Authors
  1. Noriyuki Ohara MD, PhD
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  2. Akira Morikawa MD
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  3. Wei Chen MD, PhD
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  4. Jiayin Wang MD, PhD
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  5. Deborah A. DeManno PhD
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  6. Kristof Chwalisz MD, PhD
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  7. Takeshi Maruo MD, PhD
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Corresponding author

Correspondence to Takeshi Maruo MD, PhD.

Additional information

Submitted to the Proceedings of the Eighth International Conference on the ECM of the Female Reproductive Tract (Maui, Hawaii, November 11–13, 2006)

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Ohara, N., Morikawa, A., Chen, W. et al. Comparative Effects of SPRM Asoprisnil (J867) on Proliferation, Apoptosis, and the Expression of Growth Factors in Cultured Uterine Leiomyoma Cells and Normal Myometrial Cells. Reprod. Sci. 14 (Suppl 8), 20–27 (2007). https://doi.org/10.1177/1933719107311464

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  • DOI: https://doi.org/10.1177/1933719107311464

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