Research article

Additive growth inhibitory effects of ibandronate and antiestrogens in estrogen receptor-positive breast cancer cell lines

Fabrice Journe¹ , Carole Chaboteaux¹, Nicolas Magne², Hugues Duvillier³, Guy Laurent⁴ and Jean-Jacques Body¹

¹  Laboratory of Endocrinology and Bone Diseases and Department of Internal Medicine, Institut J Bordet, Centre des Tumeurs de l'Université Libre de Bruxelles, Brussels, Belgium

²  Department of Radiotherapy, Institut J Bordet, Centre des Tumeurs de l'Université Libre de Bruxelles, Brussels, Belgium

³  Laboratory of Experimental Hematology, Institut J Bordet, Centre des Tumeurs de l'Université Libre de Bruxelles, Brussels, Belgium

⁴  Laboratory of Histology, Faculty of Medicine and Pharmacy, Université de Mons-Hainaut, Mons, Belgium

author email corresponding author email

Breast Cancer Research 2006, 8:R2doi:10.1186/bcr1363

Published:	12 December 2005

Abstract

Introduction

Bisphosphonates are inhibitors of osteoclast-mediated tumor-stimulated osteolysis, and they have become standard therapy for the management of bone metastases from breast cancer. These drugs can also directly induce growth inhibition and apoptosis of osteotropic cancer cells, including estrogen receptor-positive (ER+) breast cancer cells.

Methods

We examined the anti-proliferative properties of ibandronate on two ER+ breast cancer cell lines (MCF-7 and IBEP-2), and on one ER negative (ER-) cell line (MDA-MB-231). Experiments were performed in steroid-free medium to assess ER regulation and the effect of ibandronate in combination with estrogen or antiestrogens.

Results

Ibandronate inhibited cancer cell growth in a dose- and time-dependent manner (approximate IC₅₀: 10^-4 M for MCF-7 and IBEP-2 cells; 3 × 10^-4 M for MDA-MB-231 cells), partly through apoptosis induction. It completely abolished the mitogenic effect induced by 17β-estradiol in ER+ breast cancer cells, but affected neither ER regulation nor estrogen-induced progesterone receptor expression, as documented in MCF-7 cells. Moreover, ibandronate enhanced the growth inhibitory action of partial (4-hydroxytamoxifen) and pure (ICI 182,780, now called fluvestrant or Faslodex™) antiestrogens in estrogen-sensitive breast cancer cells. Combination analysis identified additive interactions between ibandronate and ER antagonists.

Conclusion

These data constitute the first in vitro evidence for additive effects between ibandronate and antiestrogens, supporting their combined use for the treatment of bone metastases from breast cancer.