Shime Hiroaki, Kariya Masatoshi, Orii Ayaka, Momma Chika, Kanamori Takanobu, Fukuhara Ken, Kusakari Takashi, Tsuruta Yuko, Takakura Kenji, Nikaido Toshio, Fujii Shingo
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
J Clin Endocrinol Metab. 2002 Dec;87(12):5610-7. doi: 10.1210/jc.2002-020444.
Uterine leiomyoma is a mesenchymal tumor composed of smooth muscle cells with fibrous tissues and many mast cells. Tranilast is known to suppress fibrosis or to work as a mast cell stabilizer and is reported to inhibit proliferation of vascular smooth muscle cells. In this study, we examined the effects of tranilast on cultured human leiomyoma cells in vitro to evaluate whether this agent has the potential to inhibit the growth of uterine leiomyomas. Tranilast inhibited the proliferation of cultured leiomyoma cells in a dose-dependent manner without any cytotoxic effect or induction of apoptosis. In association with the inhibitory effect, tranilast induced the cyclin-dependent kinase (CDK) inhibitor p21(waf1) and tumor suppressor gene p53 and decreased CDK2 activity. These results suggest that tranilast arrests the proliferation of uterine leiomyoma cells at the G0/G1 phase, through the suppression of CDK2 activity via an induction of p21(waf1) and p53. Tranilast was concluded to be a potent agent to inhibit proliferative activity of uterine leiomyoma cells.
子宫平滑肌瘤是一种由平滑肌细胞与纤维组织及许多肥大细胞组成的间叶组织肿瘤。曲尼司特已知可抑制纤维化或作为肥大细胞稳定剂起作用，并且有报道称其可抑制血管平滑肌细胞的增殖。在本研究中，我们在体外检测了曲尼司特对培养的人平滑肌瘤细胞的影响，以评估该药物是否具有抑制子宫平滑肌瘤生长的潜力。曲尼司特以剂量依赖性方式抑制培养的平滑肌瘤细胞的增殖，且无任何细胞毒性作用或诱导凋亡。与这种抑制作用相关，曲尼司特诱导细胞周期蛋白依赖性激酶（CDK）抑制剂p21（waf1）和肿瘤抑制基因p53，并降低CDK2活性。这些结果表明，曲尼司特通过诱导p21（waf1）和p53抑制CDK2活性，从而使子宫平滑肌瘤细胞的增殖停滞在G0/G1期。得出的结论是，曲尼司特是一种抑制子宫平滑肌瘤细胞增殖活性的有效药物。
