Evalation of Vitamin D and Doxercalciferol Effect on Uterine Fibroid Growth
Uterine fibroids (UF) are the most common pelvic tumor in women of reproductive age. Despite its high prevalence, there is an unmet need in the field for a non-hormonal fertility-friendly anti-fibroid treatment. Vitamin D deficiency has been linked to a higher risk of UF, and its efficiency as a treatment to reduce UF size has been demonstrated in vitro and in vivo. However, long-term vitamin d treatments could induce hypercalcemia, and vitamin D analogs have been proposed as an alternative since they show less calcemic activity. Our study aims to describe the signaling pathways and molecular mechanisms by which Vitamin D (VD3) and Doxercalciferol (a Vitamin D analog) (DCL) reduces UF size in a UF patient-derived xenograft (PDX). Overall design: MED12-mutant human uterine fibroids (UF) were collected from African American women undergoing hysterectomy or myomectomy for symptomatic UF (n=10). Female NOD-SCID mice (n=14) were used to generate the PDX mouse model. Mice were hormonally supplemented with 60-day release pellets with 17ß-estradiol (0.2 mg) and progesterone (50 mg). One week after the xenograft surgery, animals were treated for 6 weeks with the bioactive form of Vitamin D3 (VD3), 1a,25(OH)2D3 and the synthetic Vitamin D2 analog Doxercalciferol (DCL). According to the treatment two different studies were conducted: 1) VD3 0.5 µg/kg/day (n=3) and 2) DCL 0.3 µg/kg/day (n=4). Each study had her own control group, in which animals were treated with the corresponding drug vehicle. At the end of the treatment, animals were euthanized and UF xenografts were collected. Each study had her own control group, in which animals were treated with the corresponding drug vehicle.