Endocrine Abstracts

Several studies have addressed the possible role of leptin, the product of the obesity gene (Ob), in ovarian cancer development and progression. Herein, we used the OVCAR-3 cell line expressed both the long (ObRb) and short (ObRt) isoforms of the mRNAs of the leptin receptor, to analyse the effect of leptin on the expression of selected genes involved in the cell cycle and apoptosis. OVCAR-3 cells were exposed to 2 and 20 ng/ml of leptin (noted in non-obese women) or 40 and 100 ng/ml of leptin (noted in obese women). Cell proliferation was determined by measuring BrdU incorporation and propidium iodine DNA staining (flow cytometry). Apoptosis was measured by DNA fragmentation using the Cellular DNA Fragmentation ELISA kit and caspase-3 activity by fluorometric assay. Expression of selected genes involved in the cell cycle and apoptosis were evaluated by real-time PCR. At a physiologically relevant concentration, leptin has no effects on cell proliferation, why in concentration noted in an obese women leptin stimulated cell proliferation. 1.2- to 1.9-fold induction of genes responsible for inducing cell proliferation and a 1.2- to 1.9-fold suppression of genes responsible for inhibition of proliferation was noted. A statistically significant inhibition of caspase-3 activity and DNA fragmentation was observed under the influence of leptin at 2, 20, 40 and 100 ng/ml respectively. 1.4- to 1.8-fold suppression of genes involved in the extrinsic apoptotic pathway and a 1.2- to 2.2-fold suppression of pro-apoptotic genes involved in the intrinsic apoptotic pathway were observed. In conclusion, leptin by up-regulating genes responsible for inducing cell proliferation and down-regulating pro-apoptotic genes in extrinsic and intrinsic pathways could contribute to ovarian cancer progression. However, further research with ovarian cancer explants are needed to confirm the relationships between ovarian cancer risk and obesity.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.