title: Insulin prevents leptin inhibition of RM1 prostate cancer cell growth.
abstract: The association between obesity and cancer is controversial: whereas several epidemiological, clinical and research studies using cancer cell lines have supported that high levels of insulin and leptin could favor prostate cancer development and dissemination, other studies have demonstrated opposite effects or even absence of association. The main goal of this study was to evaluate the in vitro proliferation of murine androgen insensitive prostate carcinoma cells RM1 in the presence of leptin and insulin. After assessing and confirming the presence of leptin and insulin receptors in RM1 cells by immunocytochemistry, cells were cultured in the presence of different concentrations of leptin (0, 25, 50, 100 and 200 ng/mL), insulin (0, 50, 100, 150 and 200 nM) or leptin plus insulin ( 25 ng/ml + 50 nM; 50 ng/ml + 100 nM; 100 ng/ml + 150 nM; 200 ng/ml + 200 nM; 25 ng/ml + 150 nM; 100 ng/ml + 50 nM of leptin plus insulin, respectively). Cell proliferation was evaluated by assessing the percentage of resazurin reduction, a surrogate marker of cell metabolic rate. Leptin significantly decreased the percentage of resazurin reduction in all studied concentrations while there was only a slight or non significant difference in RM1cell proliferation in the presence of insulin or insulin combined with leptin when compared with control. These results show that leptin decreases RM1 prostate cancer cell proliferation at the studied concentrations, while insulin is able to antagonize the leptin inhibition of RM1 prostate cancer cell growth in vitro. The difference in cell growth that is modulated by the various hormonal environments may explain the heterogeneous behavior of prostate cancer in the obese human population.
authors: Department of Anatomy and UMIB (Unit for Multidisciplinary Biomedical Research) of ICBAS, University of Porto, 4099-003, Porto, Portugal.
authors: Andreia M
authors: AM
authors: Ribeiro
authors: Sofia
authors: S
authors: Pereira
authors: Sara
authors: S
authors: Andrade
authors: Madalena
authors: M
authors: Costa
authors: Carlos
authors: C
authors: Lopes
authors: Artur P
authors: AP
authors: Aguas
authors: Mariana P
authors: MP
authors: Monteiro
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004359:Drug Therapy, Combination; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin