Journal
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
Volume 213, Issue 2, Pages -Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.ajog.2015.03.055
Keywords
leiomyoma; patient-derived xenograft model; simvastatin; treatment; tumor
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Funding
- National Institutes of Health (NIH) K12 Career Development Award [5K12HD001269-12]
- NIH NCATS Grant [CTSA UL1TR000071]
- Institute for Translational Sciences at the University of Texas Medical Branch
- NIH [1R01GM081685-01, 3R01GM081685-03S1]
- University of Texas Health Science Center at Houston
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OBJECTIVE: Uterine leiomyomas represent a common gynecologic problem with no satisfactory long-term medical treatment. The purpose of this study is to examine the effects of simvastatin on uterine leiomyoma, both in vitro and in vivo. STUDY DESIGN: This is a laboratory-based experimental study. For in vitro studies, we used human and rat leiomyoma cells. For in vivo studies, we used immunodeficient mice supplemented with estrogen/progesterone pellets xenografted with human leiomyoma tissue explant. RESULTS: For in vitro studies, cells were treated with different concentrations of simvastatin for 48 hours. Simvastatin induced dose-dependent apoptosis in leiomyoma cells as measured by a fluorometric caspase-3 activity assay, and inhibited proliferation as demonstrated by an (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide) assay (both were significant at 5 and 10 mu M). In addition, simvastatin decreased Akt signaling pathway phosphorylation as examined using Western blot analysis. For in vivo studies, animals were treated for 28 days with simvastatin (20 mu g/gm body weight/day) vs vehicle control. The treatment inhibited tumor growth as measured weekly using calipers and/or ultrasound (P < .01). Finally, simvastatin decreased expression of the proliferation marker Ki67 in xenograft tumor tissue as examined by immunohistochemistry (P = .02). CONCLUSION: Simvastatin can be a promising treatment for uterine leiomyoma. Further studies, including pharmacokinetic and drug delivery studies, are required.
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