新型IKKβ激酶抑制剂的体外抗胃癌活性

目的：探究新型EF24类IKKβ激酶抑制剂H18的体外抗胃癌活性。方法：利用分子对接模拟H18与IKKβ的结合模式；利用MTT实验检测H18对胃癌细胞BGC-823抑制生长的作用；集落克隆实验检测H18对BGC-823增殖的影响；利用DAPI染色检测细胞凋亡情况；利用Western blot实验分析H18对胃癌细胞BGC-823的NF-κB信号通路的影响。结果：H18可与IKKβ的变构位点结合；H18对BGC-823细胞72 h IC50为（1.7±0.3）μmol/L；与IKK抑制剂BMS-345541相比，H18明显抑制细胞的增殖，而对凋亡无明显影响；H18可对胃癌细胞NF-κB信号通路产生明显抑制作用。结论：H18具有良好的体外抗胃癌活性，是一种具有研发前景的IKKβ抑制剂。

Anti-gastric cancer activity of novel IKKβ inhibitor in vitro

Objective: To investigate the anti-gastric cancer activity of novel IKKβ inhibitor EF24 analog H18 in vitro. Methods: Molecular docking is used to simulate the binding of H18 and IKKβ. MTT assay was used to detect the effect of H18 on the growth of gastric cancer cell line BGC-823. The clonogenicity assay was employed to investigate the role of H18 in the colony formation ability of BGC-823. Cells apoptosis was observed by DAPI staining. The inhibition of the NF-κB signaling pathway was verified by Western blot. Results: H18 binds to the allosteric site of IKKβ. The IC50 of H18 to BGC-823 cells was (1.7±0.3) μmol/L at 72 h. Compared with IKK inhibitor BMS-345541, H18 significantly inhibited cell proliferation, but had no effect on apoptosis. H18 can inhibit significantly NF-κB signaling pathway in gastric cancer cells. Conclusion: H18 is a promising IKKβ inhibitor with good anti-tumor activity in vitro.