Effect of statins combined with estradiol on the proliferation of human receptor-positive and receptor-negative breast cancer cells.
OBJECTIVE
Combination of a statin plus estrogen may reveal benefits on the cardiovascular system in postmenopausal women by additively ameliorating both the lipid profile and vascular function. Long-term therapy with estrogens, however, is associated with an increase of breast cancer risk. In contrast, evidence is accumulating that statins may inhibit carcinogenesis because of their central action on important cellular functions. It is of special clinical interest whether a statin/estrogen combination may reduce the most undesired side effect of estrogen therapy, that is, an increase in breast cancer risk. Therefore, in the present in vitro study, for the first time we have compared the effect of five statins on the proliferation of human breast cancer cells alone and in the presence of stimulatory estradiol (E(2)).


METHODS
As cell models, the receptor-positive cell line MCF-7 and the receptor-negative cell line MDA-MB 231 were used. The statins atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin were tested in the concentration range of 1.6 microm to 50 microm alone and in the range of 0.01 nm to 10 microm in combination with E(2). Cell proliferation was measured after 4 days by the adenosinetriphosphate-chemosensitivity test.


RESULTS
All statins except pravastatin were able to significantly inhibit dose dependently the cell proliferation of both cell lines. The inhibitory values were between 10% and 90%, whereby the potency was greater in the case of receptor-negative cancer cells. A significant difference in the efficacy of the statins was observed for MCF-7 cells, in which atorvastatin was less effective than the other statins. In contrast, in the presence of E(2), the statins showed similar antiproliferative actions in MCF-7 cells when tested in the concentration range of 0.01 nm to 10 microm. A reduction of cell proliferation of less than 10% was observed at the lower concentrations and between 15% and 25% at the highest concentration of 10 microm.


CONCLUSIONS
The present data indicate that statins can inhibit the proliferation of receptor-positive and -negative human breast cancer cells but failed to completely abrogate the E(2)-induced proliferation of receptor-positive breast cancer cells. Clinical trials, however, are necessary to prove this anticarcinogenic action of statins.
Mueck
Alfred O
AO
Section of Endocrinology and Menopause, Women's University-Hospital, Calwerstrasse 7, 72 076 Tuebingen, Germany. endo.meno@med.uni-tuebingen.de
Seeger
Harald
H
Wallwiener
Diethelm
D
D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000032:analysis*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004338:Drug Combinations; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011960:Receptors, Estrogen; D004958:Estradiol