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Leptin Receptor Antagonists’ Action on HDAC Expression Eliminating the Negative Effects of Leptin in Ovarian Cancer

机译:瘦素受体拮抗剂对HDAC表达的作用消除了瘦素在卵巢癌中的负面影响

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摘要

Background/Aim: A common finding in cancer cells is the overexpression of histone deacetylases (HDACs), leading to altered expression and activity of numerous proteins involved in carcinogenesis. Considering that leptin can modulate the levels of HDACs, we hypothesised that leptin receptor antagonists can alter HDAC expression. Materials and Methods: HDAC expression in cells exposed to leptin and leptin receptor antagonists (SHLA and Lan2) were evaluated in ovarian epithelial (OVCAR-3, CaOV3) and folliculoma (COV434, KGN) cells. Results: Higher HDAC expression was found in epithelial compared to folliculoma cells. Leptin increased class I and II HDACs only in OVCAR-3 cells, and SHLA was more potent then Lan-2. In folliculoma cells, leptin only increased class II HDAC expression, Lan-2 was more potent than SHLA in the COV434 and neither antagonist affected the KGN cells. Conclusion: SHLA and Lan2 eliminate the negative effects of leptin on HDAC expression in a cell-type-dependent manner. This is the first report testing leptin receptor blockers as HDAC inhibitors in ovarian cancer cells.
机译:背景/目的:癌细胞中的一个常见发现是组蛋白脱乙酰基酶(HDACs)的过表达,导致与癌变有关的许多蛋白质的表达和活性发生改变。考虑到瘦素可以调节HDAC的水平,我们假设瘦素受体拮抗剂可以改变HDAC的表达。材料和方法:在卵巢上皮细胞(OVCAR-3,CaOV3)和卵泡瘤细胞(COV434,KGN)中评估暴露于瘦素和瘦素受体拮抗剂(SHLA和Lan2)的细胞中HDAC的表达。结果:与毛囊瘤细胞相比,上皮细胞中发现了较高的HDAC表达。瘦蛋白仅在OVCAR-3细胞中增加I类和II类HDAC,SHLA比Lan-2更有效。在滤泡状瘤细胞中,瘦素仅增加II类HDAC表达,在COV434中,Lan-2比SHLA更有效,两种拮抗剂均不影响KGN细胞。结论:SHLA和Lan2以细胞类型依赖性的方式消除了瘦素对HDAC表达的负面影响。这是首次测试瘦素受体阻滞剂作为卵巢癌细胞中的HDAC抑制剂。

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