Paricalcitol, a vitamin d receptor activator, inhibits tumor formation in a murine model of uterine fibroids

Reprod Sci. 2014 Sep;21(9):1108-19. doi: 10.1177/1933719114537721. Epub 2014 Jun 12.

Abstract

We examined the antitumor and therapeutic potentials of paricalcitol, an analog of 1,25-dihydroxyvitamin D3 with lower calcemic activity, against uterine fibroids using in vitro and in vivo evaluations in appropriate uterine fibroid cells and animal models. We found that paricalcitol has potential to reduce the proliferation of the immortalized human uterine fibroid cells. For the in vivo study, we generated subcutaneous tumors by injecting the Eker rat-derived uterine leiomyoma cell line (ELT-3) rat uterine fibroid-derived cell line in athymic nude mice supplemented with estrogen pellets. These mice were administered with vehicle versus paricalcitol (300 ng/kg/d) or 1,25-dihydroxyvitamin D3 (500 ng/kg/d) for 4 consecutive weeks, and the data were analyzed. We found that while both paricalcitol and 1,25-dihydroxyvitamin D3 significantly reduced fibroid tumor size, the shrinkage was slightly higher in the paricalcitol-treated group. Together, our results suggest that paricalcitol may be a potential candidate for effective, safe, and noninvasive medical treatment option for uterine fibroids.

Keywords: 1,25-dihydroxyvitamin D3; Zemplar; leiomyoma; paricalcitol; uterine fibroids; vitamin D3.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Ergocalciferols / pharmacology*
  • Ergocalciferols / therapeutic use
  • Female
  • Humans
  • Leiomyoma / metabolism*
  • Leiomyoma / pathology
  • Leiomyoma / prevention & control
  • Mice
  • Mice, Nude
  • Random Allocation
  • Rats
  • Receptors, Calcitriol / agonists
  • Receptors, Calcitriol / metabolism*
  • Uterine Neoplasms / metabolism*
  • Uterine Neoplasms / pathology
  • Uterine Neoplasms / prevention & control
  • Vitamin D / analogs & derivatives
  • Vitamin D / pharmacology
  • Vitamin D / therapeutic use

Substances

  • Antineoplastic Agents
  • Ergocalciferols
  • Receptors, Calcitriol
  • dihydroxy-vitamin D3
  • Vitamin D
  • paricalcitol