Department of Urology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.
Department of Traditional Chinese Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China.
Biomolecules. 2024 Aug 22;14(8):1043. doi: 10.3390/biom14081043.
This study aims to explore the potential mechanisms of esculin in the treatment of renal cell carcinoma (RCC).
We employed network pharmacology to predict the potential mechanisms and targets of esculin in RCC. Molecular docking techniques were then employed to validate the predicted targets. Additionally, a series of in vitro experiments were conducted to verify the anticancer effects of esculin on RCC cells, including the CCK-8 assay, EdU assay, wound healing assay, apoptosis assay, and Western blot.
Network pharmacology and molecular docking results identified GAPDH, TNF, GSK3B, CCND1, MCL1, IL2, and CDK2 as core targets. GO and KEGG analyses suggested that esculin may influence apoptotic processes and target the PI3K/Akt pathway in RCC. Furthermore, the CCK-8 assay demonstrated that esculin inhibited RCC cell viability. Microscopic observations revealed that following esculin treatment, there was an increase in cell crumpling, a reduction in cell density, and an accumulation of floating dead cells. Additionally, with increasing esculin concentrations, the proportion of EdU-positive cells decreased, the wound closure ratio decreased, the proportion of PI-positive cells increased, the expression levels of BAX and cleaved-caspase-3 proteins increased, and the expression level of Bcl2 protein decreased. These findings suggested that esculin inhibits the proliferation and migration of RCC cells while promoting apoptosis. Moreover, esculin was found to target GAPDH and inhibit the PI3K/Akt pathway.
This study is the first to elucidate the therapeutic effects of esculin on RCC cells. The results provide evidence supporting the clinical application of esculin and introduce a promising new candidate for RCC treatment.
本研究旨在探讨七叶皂苷治疗肾细胞癌（RCC）的潜在机制。
我们采用网络药理学预测七叶皂苷治疗 RCC 的潜在机制和靶点。然后采用分子对接技术验证预测靶点。此外，还进行了一系列体外实验来验证七叶皂苷对 RCC 细胞的抗癌作用，包括 CCK-8 assay、EdU assay、伤口愈合 assay、凋亡 assay 和 Western blot。
网络药理学和分子对接结果鉴定出 GAPDH、TNF、GSK3B、CCND1、MCL1、IL2 和 CDK2 为核心靶点。GO 和 KEGG 分析表明，七叶皂苷可能影响 RCC 中的凋亡过程并靶向 PI3K/Akt 通路。此外，CCK-8 assay 表明七叶皂苷抑制 RCC 细胞活力。显微镜观察显示，七叶皂苷处理后，细胞皱缩增加，细胞密度降低，漂浮的死细胞增多。此外，随着七叶皂苷浓度的增加，EdU 阳性细胞的比例降低，伤口闭合率降低，PI 阳性细胞的比例增加，BAX 和 cleaved-caspase-3 蛋白的表达水平增加，Bcl2 蛋白的表达水平降低。这些发现表明七叶皂苷抑制 RCC 细胞的增殖和迁移，同时促进细胞凋亡。此外，七叶皂苷被发现靶向 GAPDH 并抑制 PI3K/Akt 通路。
本研究首次阐明了七叶皂苷对 RCC 细胞的治疗作用。结果为七叶皂苷在临床应用提供了证据，并为 RCC 治疗引入了一种有前途的新候选药物。
