کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3940423 | 1253587 | 2007 | 9 صفحه PDF | دانلود رایگان |
ObjectiveTo determine the potency of TKS050, a new epidermal growth factor receptor (EGFR) inhibitor and genistein, a naturally occurring protein tyrosine kinase inhibitor, to inhibit leiomyoma cell proliferation in vitro.DesignEstablishment of paired cultures of leiomyoma and normal myometrial samples.SettingUniversity clinical research laboratory.Patient(s)Hysterectomy specimens from premenopausal women affected by uterine leiomyomas.Intervention(s)The suppressive effect of TKS050 and genistein on the cells, before and after steroidal hormone treatment, was examined.Main Outcome Measure(s)Cell proliferation, recovery after treatment, cell cycle analysis, and immunochemical analysis of relevant proteins were performed.Result(s)TKS050 (2 μmol/L) and genistein (50 μmol/L) completely suppressed leiomyoma cell proliferation, and the cells did not recover after cessation of treatment. TKS050 induced cell cycle arrest and apoptosis in a dose- and time-dependent manner. Cells accumulated in the G0/G1 phase of the cell cycle at the expense of the S and G2+M phases. Treatment of cells with TKS050 resulted in a dose-dependent inhibition of EGFR autophosphorylation and of phosphorylated signal transducer and activator of transcription 3 (Stat3). Genistein inhibited the phosphorylated Stat3 but did not affect EGFR autophosphorylation. The inhibitory effects of TKS050 or genistein were unaffected by the presence of physiologic concentrations of estradiol-17β.Conclusion(s)Leiomyoma cell growth is effectively blocked by TKS050 and genistein. The inhibitory action of newly developed and natural inhibitors derived from diet may be useful as a possible alternative therapy for leiomyomas.
Journal: Fertility and Sterility - Volume 87, Issue 1, January 2007, Pages 127–135