Mostafa A Borahay1, Kathleen Vincent2, Massoud Motamedi3, Elena Sbrana4, Gokhan S Kilic5, Ayman Al-Hendy6, Darren Boehning7. 1. Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX; Department of Biochemistry and Molecular Biology, University of Texas Health Sciences Center at Houston, Houston, TX. Electronic address: maboraha@utmb.edu. 2. Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX; Biomedical Engineering Center, University of Texas Medical Branch, Galveston, TX. 3. Biomedical Engineering Center, University of Texas Medical Branch, Galveston, TX. 4. Department of Pathology, University of Texas Medical Branch, Galveston, TX. 5. Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX. 6. Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, GA. 7. Department of Biochemistry and Molecular Biology, University of Texas Health Sciences Center at Houston, Houston, TX.
Abstract
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-diphenyltetrazolium bromide) assay (both were significant at 5 and 10 μM). 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 μg/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.
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 ratleiomyoma cells. For in vivo studies, we used immunodeficient mice supplemented with estrogen/progesterone pellets xenografted with humanleiomyoma 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-diphenyltetrazolium bromide) assay (both were significant at 5 and 10 μM). 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 μg/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.
Authors: J I Germershausen; V M Hunt; R G Bostedor; P J Bailey; J D Karkas; A W Alberts Journal: Biochem Biophys Res Commun Date: 1989-02-15 Impact factor: 3.575
Authors: Birgit Assmus; Carmen Urbich; Alexandra Aicher; Wolf K Hofmann; Judith Haendeler; Lothar Rössig; Ioakim Spyridopoulos; Andreas M Zeiher; Stefanie Dimmeler Journal: Circ Res Date: 2003-04-03 Impact factor: 17.367
Authors: A Thibault; D Samid; A C Tompkins; W D Figg; M R Cooper; R J Hohl; J Trepel; B Liang; N Patronas; D J Venzon; E Reed; C E Myers Journal: Clin Cancer Res Date: 1996-03 Impact factor: 12.531
Authors: Sadia Afrin; Malak El Sabeh; Md Soriful Islam; Mariko Miyashita-Ishiwata; Minnie Malik; William H Catherino; Askar M Akimzhanov; Darren Boehning; Qiwei Yang; Ayman Al-Hendy; James H Segars; Mostafa A Borahay Journal: Pharmacol Res Date: 2021-08-28 Impact factor: 10.334
Authors: Mostafa A Borahay; Xiao Fang; Jacques G Baillargeon; Gokhan S Kilic; Darren F Boehning; Yong-Fang Kuo Journal: Am J Obstet Gynecol Date: 2016-06-28 Impact factor: 8.661
Authors: Phyllis C Leppert; Ayman Al-Hendy; Donna D Baird; Serdar Bulun; William Catherino; Darlene Dixon; Merrick Ducharme; Quaker E Harmon; Friederike L Jayes; Emmanuel Paul; Aymara Mas Perucho; James Segars; Carlos Simón; Elizabeth A Stewart; Jose Teixeira; Andrea Tinelli; Daniel Tschumperlin; Ami R Zota Journal: F S Sci Date: 2020-11-07