Abstract A139: Effects of simvastatin and of a cyclic nonapeptide derived from alpha fetoprotein on the proliferation of ERα-positive mammary tumor cells in culture

Abstract

Abstract Introduction: Estradiol (E2) stimulate the progression of many mammary tumors, including those of dogs, by association to estrogen receptors (ER). We have recently reported on the effects of E2 and of an AFP-derived cyclized peptide (cP) on the proliferation of cancer cells from different mammalian species demonstrating that, in ER-positive cells, estradiol increased cell proliferation and the phosphorylation of ERK 1/2; these effects were effectively inhibited by the presence of cP in the culture medium. It has been reported that statins restrain the proliferation in culture of mammary tumor cells. We report here on the effects of statins and cP on the estrogen-stimulated proliferation of mammary tumor cells. Aims: Evaluate the proliferation on mammary tumor cells after exposure to E2, without / with cP and simvastatin; comparison with the effect of ICI 182,780 (ICI). Methods: MCF7 cells grown in DMEM F12 containing ITS (insulin, transferrin, selenium), 1% charcoal/dextran-twice-treated calf serum, 3% hydroxyethilated starch (HAES) and antibiotics were incubated of estradiol in the absence and presence of cP and various concentrations of simvastatin. Cell proliferation measurement and the assessment of viability (trypan blue) was done by haemocytometry. Results and Conclusions: The proliferation of control (unstimulated) MCF7 cells, was not affected by the presence of either simvastatin or cP in the culture medium. The addition of 2nM E2 significantly increased the proliferation rate of the cells. The effect was reduced by cP to basal values, i.e. to the same extent than the specific antagonist ICI does. At the concentrations used, simvastatin had no effect on the proliferation of MCF7 cells stimulated with estradiol. We suggest that the effects of cP on the proliferation of estradiol-stimulated MCF7 cells are probably not related with a prenylation of ER. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A139.