Evaluation of human breast adenocarcinoma [MCF-7] cells proliferation in co-culture with human adipocytes in three dimensional collagen gel matrix: norepinephrine as a lipolytic factor

ABSTRACT

Norepinephrine plays a trophic role in the control of cell replication and differentiation in target cells that express adrenergic receptors. In this study, we have tested the influence of infraphysiological, physiological and supraphysiological concentrations [0.0001 nM, 1 nM, 10000 nM] of human norepinephrine on the proliferation of breast cancer cells [human breast adenocarcinoma [MCF-7]] in co-culture with human adipocytes in three-dimensional collagen gel matrix culture. Cell proliferation and lipolysis rate were measured by 3-[4, 5-dimethylthiazolyl]-2, 5-diphenyl-tetrazolium bromide [MTT] and Oil red O colorimetric assay in second, 7[th] and 14[th] days of culture experiments. Our results showed a direct correlation between lipolysis rate of adipocytes and proliferation rate of MCF-7 cells. Both physiological and supraphysiological concentrations of human norepinephrine significantly [P<0.05] increased the proliferation of MCF-7 cells synchronously with progress of adipocyte lipolysis. The proliferations of MCF-7 cells were significantly decreased after conversion of adipocytes to fibroblast-like cells by supraphysiological concentration of norepinephrine. There was no statistical difference in lipolysis of adipocytes and proliferation of MCF-7 cells in response to infraphysiological concentration of norepinephrine. These findings indicated that norepinephrine stimulated the proliferation of MCF-7 cells in co-culture with human adipocytes as a lipolytic factor and that norepinephrine effect was suppressed by conversion of adipocytes to fibroblast-like cells, suggesting adipocytes as another target for prevention and therapy of breast cancer