1,25-Dihydroxyvitamin D3 Treatment Shrinks Uterine Leiomyoma Tumors in the Eker Rat Model

Sunil K. Halder, Chakradhari Sharan, Ayman Al-Hendy

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Uterine leiomyomas (fibroids) are the most common benign tumors in women of reproductive age. These tumors are three to four times more prevalent in African American women, who also have a 10 times higher incidence of hypovitaminosis D than white women. Recent studies have demonstrated the antitumor effects of 1,25-dihydroxyvitamin D3 on several cancers, but its effects on uterine leiomyomas are still unknown. To determine the antitumor and therapeutic effects of 1,25-dihydroxyvitamin D3 on uterine leiomyomas, female Eker rats (14-16 mo old) harboring uterine leiomyomas were randomized into control and experimental groups and were given vehicle versus 1,25-dihydroxyvitamin D3 (0.5 lg/kg per day) subcutaneously for 3 wk, respectively. At the end of the experiment, the rats were euthanized, and the leiomyoma tumors were analyzed. Treatment with 1,25-dihydroxyvitamin D3 significantly reduced leiomyoma tumor size in Eker rats. It also reduced leiomyoma size by suppressing cell growth and proliferation-related genes (Pcna, cyclin D1 [Ccnd1], Myc, Cdk1, Cdk2, and Cdk4), antiapoptotic genes (Bcl2 and Bcl2l1 [Bcl-x]), and estrogen and progesterone receptors. Additionally, immunohistochemistry revealed decreased expression of PCNA and MKI67 (a marker of proliferation) and increased expression of caspase 3 in 1,25-dihydroxyvitamin D3-treated Eker rat leiomyomas. Toxicity analyses using serum samples showed similar levels of SGOT, SGPT, calcium, and total bilirubin in 1,25-dihydroxyvitamin D3-treated and vehicletreated control Eker rats. These results support that 1,25- dihydroxyvitamin D3 is an antitumor agent that may be a potential safe, nonsurgical therapeutic option for the treatment of uterine leiomyomas.

Original languageEnglish (US)
Article number116
JournalBiology of reproduction
Volume86
Issue number4
DOIs
StatePublished - Apr 1 2012

Fingerprint

Calcitriol
Leiomyoma
Neoplasms
Therapeutics
bcl-1 Genes
Proliferating Cell Nuclear Antigen
Therapeutic Uses
Progesterone Receptors
Aspartate Aminotransferases
Alanine Transaminase
Bilirubin
Caspase 3
Estrogen Receptors
African Americans
Antineoplastic Agents
Immunohistochemistry
Cell Proliferation
Calcium
Control Groups

Keywords

  • 1,25-dihydroxyvitamin D3
  • Eker rats
  • Fibroids
  • Leiomyoma
  • Radioimmunoassay

ASJC Scopus subject areas

  • Cell Biology

Cite this

1,25-Dihydroxyvitamin D3 Treatment Shrinks Uterine Leiomyoma Tumors in the Eker Rat Model. / Halder, Sunil K.; Sharan, Chakradhari; Al-Hendy, Ayman.

In: Biology of reproduction, Vol. 86, No. 4, 116, 01.04.2012.

Research output: Contribution to journalArticle

Halder, Sunil K. ; Sharan, Chakradhari ; Al-Hendy, Ayman. / 1,25-Dihydroxyvitamin D3 Treatment Shrinks Uterine Leiomyoma Tumors in the Eker Rat Model. In: Biology of reproduction. 2012 ; Vol. 86, No. 4.
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