目的 研究沙苑子苷A潜在的抗肿瘤作用。方法 利用计算机模拟方法，采用Discovery Studio^TM 4.0（DS）软件反向寻靶，初步探讨沙苑子苷A潜在的抗肿瘤靶点，并通过CDOCKER进行分子对接初步验证结果；建立体外鸡胚绒毛尿囊膜（CAM）模型实验，血管计数法观察沙苑子苷A（0.2、0.4、0.8 mg/mL）对CAM新生血管生成的影响。结果 反向寻靶结果表明，沙苑子苷A可调控原癌基因酪氨酸蛋白激酶（ABL1）、原癌基因酪氨酸蛋白激酶（SRC）、靶点蛋白纤维生长因子受体1（FGFR1）、纤维生长因子受体（FGFR2）和转化生长因子-β（TGF-β）；分子对接结果证明，沙苑子苷A能够调控血管生长相关靶点；体外CAM实验结果发现，与对照组比较，沙苑子苷A能显著抑制新生中、小血管的生成（P<0.05、0.01）。结论沙苑子苷A可能是沙苑子发挥抗肿瘤作用的主要活性成分，可能通过调控肿瘤基因的表达和抑制新生血管的生成发挥作用。

Objective To study the potential anti-tumor effect of complanatoside A. Methods Target Searching of the anti-tumor protein correlated with complanatoside A based on reverse seeking target method, and further validated the target protein through the CDOCKER molecular docking approach. Finally, to validate neovascularization of complanatoside A (0.2, 0.4 and 0.8 mg/mL), the model of chick embryo chorioallantoic membrane was established. Results DS reverse seeking target found that the protooncogene of ABL1, SRC and 3 protein of FGFR1, FGFR2 and TGF-β, which were involved in tumor angiogenesis, were regulated by complanatoside A. Moreover, complanatoside A significantly inhibited small blood and medium vessels growth in Chick Embryo CAM model (P < 0.05 or 0.01). Conclusion The results suggested that CA might be an anti-tumor active ingredient of Astragalus complanatus. The anti-tumor mechanism of CA was involving in regulating the tumors gene expression and significantly suppressing angiogenesis in Chick Embryo CAM model.

R962

国家“重大新药创制”科技重大专项（2019ZX09735-002）