In vitro and in vivo biologic effects of Ospemifene (FC-1271a) in breast cancer

J Steroid Biochem Mol Biol. 2001 Jun;77(4-5):271-9. doi: 10.1016/s0960-0760(01)00066-8.


Ospemifene (FC-1271a) is a novel selective estrogen receptor modulator under development for osteoporosis prevention. In the present paper, we examine both the in vitro and in vivo effects of FC-1271a in breast cancer models. In vitro, the growth inhibitory effects of FC-1271a and its main metabolite are investigated in MCF-7 and MDA-MB-231 human breast cancer cells at doses ranging from 0.1 to 10 microM. Modulation of pS2 expression, an indicator of estrogen activity, was also examined in all experiments using reverse transcription-polymerase chain reaction. In vivo, the effects of treatment with 10, 25, 50, or 100 mg/kg FC-1271a on MCF-7 and MDA-MB-231 human tumor xenografts in athymic, ovariectomized mice were determined. For MCF-7 cells, FC-1271a and its main metabolite, toremifene VI (TOR VI) displayed anti-estrogenic effects in vitro as shown through growth inhibition and decreased expression of pS2. Treatment with FC-1271a in vivo inhibited MCF-7 tumor growth, compared with control (P< or =0.05). FC-1271a and TOR VI did not inhibit the growth of MDA-MB-231 cells in vitro, and no clear effects of FC-1271a treatment were seen on MDA-MB-231 tumor growth in vivo. In conclusion, FC-1271a appears to exert anti-estrogenic effects dependent on estrogen receptor positivity in vitro and in vivo on the growth of MCF-7 cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Division / drug effects
  • Chromatography, High Pressure Liquid
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / drug effects
  • Disease Models, Animal
  • Estrogen Antagonists / pharmacokinetics
  • Estrogen Antagonists / pharmacology
  • Estrogen Antagonists / therapeutic use*
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / prevention & control*
  • Polymerase Chain Reaction
  • RNA, Neoplasm / drug effects
  • Selective Estrogen Receptor Modulators / pharmacokinetics
  • Selective Estrogen Receptor Modulators / pharmacology
  • Selective Estrogen Receptor Modulators / therapeutic use*
  • Tamoxifen / analogs & derivatives
  • Tamoxifen / pharmacokinetics
  • Tamoxifen / pharmacology
  • Tamoxifen / therapeutic use*
  • Transplantation, Heterologous
  • Tumor Cells, Cultured


  • DNA, Complementary
  • Estrogen Antagonists
  • RNA, Neoplasm
  • Selective Estrogen Receptor Modulators
  • Tamoxifen
  • Ospemifene