牛蒡苷元抗肿瘤潜在靶点预测及验证

Prediction and verification of potential antitumor target of arctigenin

目的研究牛蒡苷元潜在抗肿瘤作用靶点。方法以id Target反向分子对接在线服务器为工具预测牛蒡苷元潜在抗肿瘤作用靶点,采用正向分子对接分析其相互作用,并进一步进行体外分子水平和细胞水平试验验证对接结果。结果反向分子对接结果显示牛蒡苷元能够较好地与肝细胞生长因子受体c-Met结合,预测结合常数Ki值为248 nmol·L-1(PDB ID:3EFK);正向分子对接结果显示牛蒡苷元与靶点存在合理的氢键相互作用;酶联免疫法测定牛蒡苷元100 nmol·L-1水平对受体酪氨酸激酶c-Met酶活抑制率为47.5%;磺酰罗丹明B蛋白染色法测定牛蒡子苷元对非小细胞肺癌细胞株(EBC-1)增殖抑制的IC50值为(201.7±19.8)nmol·L-1。结论 c-Met是牛蒡苷元抗肿瘤作用的潜在靶点。

Objective To dig out the potential antitumor target of arctigenin. Methods The id Target web server was used as a tool to forecast the potential antitumor target of arctigenin,and the result could be well analyzed by forward-docking. Furthermore,the in vitro molecular level and cell level experiments were carried out to verify the result from molecular dockings. Results Molecular reverse-docking showed that arctigenin could well bind to c-Met,a hepatocyte growth factor receptor,and the predicted binding constant Ki was 248 nmol·L^-1（ PDB ID： 3EFK）. Forward-docking indicated that interaction between arctigenin and target through hydrogen bonds was reasonable. ELISA confirmed that activity inhibition rate of arctigenin against c-Met enzyme was 47. 5% at 100 nmol·L^-1. in vitro experiments with the method of sulforhodamine BSRB showed that the IC50 value of proliferation inhibition on non-small cell lung cancer cell（ EBC-1） by arctigenin was（ 201. 7 ± 19. 8） nmol·L^-1. Conclusions C-Met is a potential antitumor target of arctigenin.