According to the World Health Organization, the incidence and mortality rates of renal cell carcinoma (RCC) are rapidly increasing worldwide. Serious side effects caused by immune therapy and resistance to targeted drug therapy are urgent clinical problems facing kidney treatment. There is increasing global interest in developing natural products with a reduced number of side effects as adjunctive therapeutic options for RCC. Ginger is a spice and herbal remedy used worldwide, and 6‐gingerol is a major pharmacologically active ingredient in ginger. In our study, we found that 6‐gingerol suppressed RCC cell migration and metastasis in vitro and in vivo. Moreover, reduction in MMP2, Slug, and Vimentin protein levels was observed following 6‐gingerol treatment of 786‐O and ACHN cells. Furthermore, we revealed the mechanisms underlying the ability of 6‐gingerol to inhibit RCC cell migration and metastasis. 6‐Gingerol increased yes‐associated protein (YAP)^ser127 phosphorylation and reduced YAP levels in cell nuclei. We also used a series of loss‐of‐function and gain‐of‐function experiments to support our results. Western blot results showed that MMP2, Slug, and Vimentin protein expression was downregulated in YAP‐silenced cells and upregulated in YAP‐overexpressing cells. Transwell data demonstrated that YAP suppressed RCC migration ability. Immunofluorescence images showed that 6‐gingerol decreased YAP levels, leading to disordered F‐actin and a reduction in cell lamellipodia. Overall, our results indicated that 6‐gingerol is a potential antimetastatic compound for use in kidney therapy.

中文翻译：

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6-Gingerol 通过增加肾细胞癌中 YAPser127 磷酸化来抑制肿瘤细胞转移。


据世界卫生组织称，全球范围内肾细胞癌（RCC）的发病率和死亡率正在迅速上升。免疫治疗引起的严重副作用和对靶向药物治疗的耐药性是肾脏治疗面临的紧迫临床问题。全球越来越有兴趣开发副作用较少的天然产品作为肾细胞癌的辅助治疗选择。生姜是一种世界各地使用的香料和草药，6-姜酚是生姜中的主要药理活性成分。在我们的研究中，我们发现 6-姜酚在体外和体内抑制肾细胞癌细胞的迁移和转移。此外，用 6-姜酚处理 786-O 和 ACHN 细胞后，观察到 MMP2、Slug 和 Vimentin 蛋白水平降低。此外，我们还揭示了 6-姜酚抑制肾细胞癌细胞迁移和转移的机制。 6-姜酚增加 yes 相关蛋白 (YAP) ^ser127磷酸化并降低细胞核中的 YAP 水平。我们还使用了一系列功能丧失和功能获得实验来支持我们的结果。 Western blot结果显示，MMP2、Slug和Vimentin蛋白表达在YAP沉默细胞中下调，而在YAP过表达细胞中上调。 Transwell数据表明YAP抑制RCC迁移能力。免疫荧光图像显示，6-姜酚降低了 YAP 水平，导致 F-肌动蛋白紊乱和细胞片状伪足减少。总的来说，我们的结果表明 6-姜酚是一种用于肾脏治疗的潜在抗转移化合物。