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

Background: Norepinephrine plays a trophic role in the control of cell replication and differentiation in target cells that express adrenergic receptors. Methods: 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, 7th days of culture experiments. Results: 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. Conclusion: These findings indicated that norepinephrine stimulated the proliferation of MCF-7 cells in coculture 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.