Abstract
Uterine leiomyoma (fibroids) are benign tumors in the uterus of reproductive age women. African American women have three to four times more fibroids as well as they have ten times more hypovitaminosis D than white women. However, it is not well studied whether vitamin D3 has any association with leiomyoma growth. The Eker rats represent an excellent pre-clinical model for evaluating therapeutic strategies for the treatment of leiomyoma. Recently we presented preliminary data of the ability of 1, 25-dihydroxyvitamin D3 (VitD3) treatment to shrink fibroid lesions in Eker rats. In this work we provide additional clinical and molecular characterization of the effect of VitD3 on uterine fibroids. The therapeutic effect of VitD3 was examined in Eker rats spontaneous model for leiomyoma. Leiomyomas in female Eker rats were confirmed by a limited laparotomy aseptically under anesthesia. Tumor-harboring rats were treated with VitD3 at the dose of 0.5 μg/Kg/day for 21 days. Rats were sacrificed, leiomyoma tumors were measured, and tissue samples were used for immunohistochemistry and western blots for molecular evaluation. VitD3 suppressed leiomyoma growth by reducing proliferation marker such as PCNA, Ki67, Cdk1, Cdk2, and Cdk4. Immunohistochemistry showed induced expression of caspase-3 by VitD3 treatment. Liver function analyses by measuring serum levels of SGPT, SGOT, and total bilirubin showed no significant changes between vehicle-control and VitD3-treated rats. H&E staining of liver and kidney showed similar staining pattern between vehicle-control and VitD3-treated rats. Serum levels of calcium were similar between those two groups, suggesting the dose used is therapeutically safe and non-toxic. Together our results suggest the potent anti-tumor function of VitD3 on reduction of leiomyoma growth in Eker rats. VitD3 might be a potent and safe therapeutic agent for non-surgical treatment of leiomyoma.
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