Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Germany, Marchioninistr. 15, 81377, Munich, Germany.
Institute of Pathology, University Hospital, LMU Munich, Germany, Marchioninistr. 15, 81377, Munich, Germany.
Arch Gynecol Obstet. 2022 Jun;305(6):1559-1572. doi: 10.1007/s00404-021-06262-w. Epub 2021 Dec 6.
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 gynaecologic cancers. Furthermore, RSV targets Sirtuin1 (Sirt1), a histone deacetylase.
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 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) 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.
卵巢癌是最致命的妇科癌症。白藜芦醇（RSV）已知会改变癌症中的代谢。它影响核视黄醇 X 受体（RXR），这意味着 RXR 对妇科癌症具有调节作用。此外，RSV 靶向 Sirtuin1（Sirt1），一种组蛋白去乙酰化酶。
检查了 123 例浆液性或黏液性卵巢癌患者的 Sirt1 和 RXR 表达情况。用 RSV 处理卵巢细胞系，并评估其对活力和凋亡的影响。通过 Western blot 分析 RSV 对 Sirt1 和 RXR 表达的影响。
可以检测到核 Sirt1 和 RXRα表达之间的相关性（p=0.006）。核 RXRα和细胞质（p=0.026）或核（p=0.041）Sirt1 的共表达与晚期肿瘤阶段总生存率的显著增加相关。在所有细胞系中，用 RSV 刺激后，细胞活力降低，而细胞凋亡增加。RSV 处理导致 A2780 细胞中 Sirt1 表达显著降低（p=0.025），cisA2780 细胞中 RXR 表达显著增加（p=0.012）。
为了将 RSV 用作医学靶点，可以开展研究来提高对耐药机制的理解，从而改善治疗效果。
