The role of Resveratrol, Sirtuin1 and RXRα as prognostic markers in ovarian cancer
Abstract Objective: Ovarian cancer is the most lethal gynecologic cancer. Resveratrol (RSV) is known to alter metabolism in cancer. It affects the nuclear retinoid-X-receptor (RXR), which implies a modulating effect of RXR to gynecologic cancers. Furthermore, RSV targets Sirtuin1 (Sirt1), a histone deacetylase. Study design: 123 tissue samples of patients with serous or mucinous ovarian cancer were examined for expression of Sirt1 and RXR. Ovarian cell-lines were treated with RSV and consequences on viability and apoptosis were evaluated. The influence of RSV to Sirt1 and RXR expression was analyzed by western blotting. Results: A correlation of nuclear Sirt1 and RXRα expression could be detected (p=0.006). Co-expression of nuclear RXRα and cytoplasmic (p=0.026) or nuclear (p=0.041) Sirt1 was associated with significantly increased overall survival in advanced tumor stages. Viability was decreased in all cell-lines after stimulation with resveratrol, while cell apoptosis was increased. RSV treatment led to significant lower Sirt1 expression in A2780 cells (p=0.025) and significant increased RXR expression in cisA2780 cells (p=0.012). Conclusion: In order to use RSV as medical target, studies could be developed to improve the understanding of drug resistance mechanisms and consequently improve treatment outcome.