【摘要】 目的 研究佛手柑内酯（bergapten,BeG）抑制胃癌细胞增殖的作用机制。方法 联合网络药理学和生物信息学筛选出在胃癌中BeG可能的重要靶点; CCK-8试剂盒和克隆形成实验检测不同剂量BeG处理胃癌细胞后，细胞增殖能力的变化;构建稳定敲低花生四烯酸-5-脂加氧酶（arachidonic acid-5-lipoxygenase,ALOX5）的SGC-7901、BGC-823细胞系，CCK-8试剂盒和克隆形成实验检测其增殖能力的变化;免疫印迹（Western blot,WB）检测ALOX5、Ki67蛋白表达水平;构建胃癌移植瘤模型，检测BeG对肿瘤生长的影响;恢复ALOX5蛋白表达水平，CCK-8实验检测BeG对胃癌细胞活性的影响，WB检测Ki67蛋白表达。结果 在BeG的45个靶点中，ALOX5既在胃癌中高表达，又影响胃癌的总生存期，且与胃癌远端转移相关; BeG在体内外均能抑制SGC-7901、BGC-823细胞增殖和Ki67蛋白表达;敲低ALOX5后，SGC-7901、BGC-823细胞增殖能力明显减弱;恢复ALOX5蛋白表达水平后，BeG的抑癌能力被逆转。结论 ALOX5是BeG的重要靶点，BeG通过ALOX5抑制胃癌细胞增殖。更多还原

【Abstract】 Objective To investigate the mechanism of bergapten( BeG) on the proliferation of gastric cancer cells. Methods The possible important targets of BeG in gastric cancer were screened by netw ork pharmacology and bioinformatics. CCK-8 and clone formation assay were used to detect the proliferation ability of SGC-7901/BGC-823 cells after different doses of BeG.SGC-7901 and BGC-823 cell lines of stably knocking down ALOX5 were established,and CCK-8 and clone formation assay were used to detect the proliferation ability. The levels of ALOX5 and Ki67 were detected by Western blot( WB). The animal model of SGC-7901 cell subcutaneous tumor transplantation was established to observe the effect of BeG on tumor growth. The level of ALOX5 protein was restored,and the effect of BeG on SGC-7901/BGC-823 cells was detected by CCK-8 assay.Results Among the 45 targets of BeG,ALOX5 was not only higher in gastric cancer,but also affected the overall survival time,and was associated with distal metastasis. BeG inhibited the proliferation and Ki67 protein level of gastric cancer cells in vitro and in vivo. After knockdown of ALOX5,the proliferation ability of SGC-7901 and BGC-823 cells was decreased significantly.After ALOX5 level restored,the anti-tumor ability of BeG was reversed. Conclusion ALOX5 is an important target of BeG.BeG inhibits the proliferation of gastric cancer cells through ALOX5.更多还原