Long-term vitamin D treatment decreases human uterine leiomyoma size in a xenograft animal model

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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.


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