Abstract
ObjectiveOvarian 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 gynaecologic cancers. Furthermore, RSV targets Sirtuin1 (Sirt1), a histone deacetylase.Study design123 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 blottingResultsA 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 tumour 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)ConclusionIn order to use RSV as medical target, studies could be developed to improve the understanding of drug resistance mechanisms and consequently improve treatment outcome.
Highlights
Ovarian cancer is the most lethal gynaecologic malignancy and the eighth leading cause of cancer-related mortality among women worldwide [1, 2]
We immunohistochemically examined the expression of RXRα and Sirt1 in mucinous and serous ovarian cancer and analyzed the relationship between RSV, RXRα and Sirt1 in ovarian cancer in vitro
Considering the potential medical role of resveratrol in ovarian cancer, we evaluated the effects of RSV by proliferation and apoptosis experiments
Summary
Ovarian cancer is the most lethal gynaecologic malignancy and the eighth leading cause of cancer-related mortality among women worldwide [1, 2]. It has been confirmed that RSV improves the efficacy of cisplatin in ovarian cancer [8]. RSV is able to modulate vitamin D receptor (VDR)-signaling and it can induce dimerization of VDR with one of its partners, the nuclear retinoid X receptor (RXR) [9]. The distribution of RXR subtypes is different, their functions are similar: modulating gene expression they control numerous functions by dimerization with other nuclear hormone receptors, contributing thereby to activities of different cell fates [13]. As the VDR is known to be involved in gynaecologic cancers, the interaction of VDR with the RXR implies that the RXR may have a modulating effect on gynaecological cancers [14]
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