%0 Journal Article
%T Additive growth inhibitory effects of ibandronate and antiestrogens in estrogen receptor-positive breast cancer cell lines
%A Fabrice Journe
%A Carole Chaboteaux
%A Nicolas Magne
%A Hugues Duvillier
%A Guy Laurent
%A Jean-Jacques Body
%J Breast Cancer Research
%D 2005
%I BioMed Central
%R 10.1186/bcr1363
%X 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.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 ¡Á 10-4 M for MDA-MB-231 cells), partly through apoptosis induction. It completely abolished the mitogenic effect induced by 17¦Â-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.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.Over 80% of women suffering from advanced breast cancer ultimately develop bone metastases [1,2]. As revealed by observations published more than a decade ago [3], patients with estrogen receptor (ER)-positive neoplasms are more prone to develop skeletal secondaries. Metastatic breast cancer cells stimulate osteoclast-mediated bone resorption, inducing a marked osteolysis that is responsible for considerable morbidity [4,5].Bisphosphonates are potent inhibitors of osteoclast-mediated osteolysis [6] and have, therefore, emerged as a rational approach for the management of bone metastases [7,8]. These drugs are synthetic analogs of pyrophosphate. They show high affinity for bone mineral and preferentially accumulate at sites of active bone remodeling. Th
%U http://breast-cancer-research.com/content/8/1/R2