Wu Yuqi, Yang Yue, Huang Run, Li Tao, Wan Chunlei, Zhang Lei
School of Life Science and Technology, Mudanjiang Normal University, Mudanjiang 157011, China.
Biology (Basel). 2024 Dec 19;13(12):1064. doi: 10.3390/biology13121064.
In this study, we investigated the effect and mechanism of Resibufogenin on renal cell carcinoma based on network pharmacology, molecular docking, and in vitro experiments. The results showed that there were 35 cross-targets between Resibufogenin and renal cell carcinoma. GO and KEGG pathway analyses indicated that Resibufogenin inhibited renal cancer cells through the vascular smooth muscle contraction signalling pathway and EGFR tyrosine kinase inhibitor resistance signaling pathway, and MAPK1, PRKCB, and Resibufogenin had strong associative activities. After different concentrations of Resibufogenin were applied to human renal cancer cells, it was found that the IC50 value was 408.2 nM, 10 nM resibufogenin could significantly inhibit cell migration ( < 0.0001), the percentage of apoptosis and necrosis increased dose-dependently, and the expression of genes of MAPK1 and PRKCB in the cells was significantly reduced ( < 0.001) in a dose-dependent manner. The above results indicate that Resibufogenin can inhibit human renal cell carcinoma through multi-targets and multi-methods, which provides a theoretical basis for the application of Resibufogenin in the treatment of renal cell carcinoma and the development of novel drugs in the future.
在本研究中，我们基于网络药理学、分子对接和体外实验，研究了华蟾毒精对肾细胞癌的作用及机制。结果显示，华蟾毒精与肾细胞癌之间存在35个交叉靶点。基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析表明，华蟾毒精通过血管平滑肌收缩信号通路和表皮生长因子受体（EGFR）酪氨酸激酶抑制剂抗性信号通路抑制肾癌细胞，且丝裂原活化蛋白激酶1（MAPK1）、蛋白激酶Cβ（PRKCB）与华蟾毒精具有较强的关联活性。将不同浓度的华蟾毒精作用于人类肾癌细胞后，发现其半数抑制浓度（IC50）值为408.2 nM，10 nM华蟾毒精可显著抑制细胞迁移（P<0.0001），凋亡和坏死百分比呈剂量依赖性增加，细胞中MAPK1和PRKCB基因的表达呈剂量依赖性显著降低（P<0.001）。上述结果表明，华蟾毒精可通过多靶点、多途径抑制人肾细胞癌，为华蟾毒精在肾细胞癌治疗中的应用及未来新型药物的研发提供了理论依据。
