Antiproliferative effects of anastrozole, methotrexate, and 5-fluorouracil on endometriosis in vitro and in vivo

Fertil Steril. 2010 Oct;94(5):1632-8.e1. doi: 10.1016/j.fertnstert.2009.09.031. Epub 2010 Jan 4.

Abstract

Objective: To investigate the effects of antiproliferative drugs (anastrozole, methotrexate, and 5-fluorouracil [5-FU]) on the proliferation of endometriotic cells in vitro and in vivo.

Design: Ex vivo study on human endometrial and endometriotic cells in culture; establishment of a murine model using mice implanted with human endometriosis.

Setting: University research center.

Patient(s): Ten patients with ovarian endometrioma, 10 patients with deep infiltrating endometriosis, and 10 patients without endometriosis.

Intervention(s): Stromal and epithelial cells were extracted from endometrial and endometriotic biopsies from patients with endometriosis and from patients without endometriosis. Cells were treated in vitro with anastrozole, methotrexate, progesterone, or 5-FU. Human endometriotic lesions were implanted in nude mice. Mice were treated with 5-FU or phosphate-buffered saline during 4 weeks before sacrifice and extraction of the endometriotic implants.

Main outcome measure(s): Stromal and epithelial cell proliferation and pathology score of endometriotic implants.

Result(s): Although anastrozole, methotrexate, and progesterone were ineffective, 5-FU significantly decreased the proliferation of endometriotic cells in vitro and controlled the growth of both cells from ovarian endometrioma and deep infiltrating endometriosis.

Conclusion(s): Considering common features between endometriotic cells and tumor cells, the use of 5-FU could be an option in the management of severe endometriosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anastrozole
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Biopsy
  • Case-Control Studies
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Endometriosis / drug therapy
  • Endometriosis / pathology*
  • Endometrium / drug effects
  • Endometrium / pathology
  • Female
  • Fluorouracil / pharmacology*
  • Fluorouracil / therapeutic use
  • Humans
  • Methotrexate / pharmacology*
  • Mice
  • Mice, Nude
  • Nitriles / pharmacology*
  • Progesterone / pharmacology
  • Transplantation, Heterologous
  • Triazoles / pharmacology*
  • Uterine Diseases / drug therapy
  • Uterine Diseases / pathology*

Substances

  • Antineoplastic Agents
  • Nitriles
  • Triazoles
  • Anastrozole
  • Progesterone
  • Fluorouracil
  • Methotrexate