Long-term vitamin D treatment decreases human uterine leiomyoma size in a xenograft animal model
Vitamin D short-term treatment maintains human leiomyoma size in a xenograft model, and long term significantly reduces it by inhibiting proliferation and increasing extracellular matrix degradation and apoptosis without side-effects.
Volume 113, Issue 1, Pages 205–216.e4
Authors:
Ana Corachán, M.Sc., Hortensia Ferrero, Ph.D., Julia Escrig, M.D., Javier Monleon, M.D., Ph.D., Amparo Faus, B.Sc., Irene Cervelló, Ph.D., Antonio Pellicer, M.D., Ph.D.
Abstract:
Objective
To study the effects of short- and long-term vitamin D treatment on uterine leiomyomas in vivo through cell proliferation, extracellular matrix (ECM) degradation, and apoptosis.
Design
Preclinical study of human leiomyoma treatment with vitamin D in an nonhuman animal model.
Setting
Hospital and university laboratories.
Patient(s)/Animal(s)
Human leiomyomas were collected from patients and implanted in ovariectomized NOD-SCID mice.
Intervention(s)
Mice were treated with vitamin D (0.5 μg/kg/d or 1 μg/kg/d) or vehicle for 21 or 60 days.
Main Outcome Measure(s)
Vitamin D effect in xenograft tissue was assessed by monitoring tumor size (18F-FDG positron-emission tomography/computerized tomography and macroscopic examination), cell proliferation (immunohistochemistry and quantitative real-time polymerase chain reaction [qRT-PCR]), ECM (Western blot), transforming growth factor (TGF) β3 (qRT-PCR), and apoptosis (Westrn blot and TUNEL).
Result(s)
Short-term treatment with vitamin D did not appear to alter leiomyoma size, based on in vivo monitoring and macroscopic examination. However, long-term high-dose treatment induced a significant reduction in leiomyoma size. Cell proliferation was not decreased in the short term, whereas 1 μg/kg/d vitamin D in the long term significantly reduced proliferation compared with control. Although collagen-I and plasminogen activator inhibitor 1 were not modified by short-term treatment, they were both significantly reduced by long-term high-dose vitamin D. Similarly, long-term high-dose vitamin D significantly reduced TGF-β3 expression. Finally, apoptosis significantly increased with both short- and long-term high-dose vitamin D treatment.
Conclusion(s)
Long-term vitamin D acts as an antiproliferative, antifibrotic, and proapoptotic therapy that provides a safe, nonsurgical therapeutic option for reducing uterine leiomyoma size without side-effects.
