鸦胆子对非小细胞肺癌细胞增殖的影响及机制

Effects of Brucea javanica on the proliferation of non-small cell lung cancer cells and its mechanism

目的:研究鸦胆子对非小细胞肺癌增殖的影响及其机制。方法:通过网络药理学分析获取鸦胆子有效成分及其相关抗肿瘤靶点;利用GeneCards数据库,获得鸦胆子治疗非小细胞肺癌的潜在靶点;借助String在线平台对鸦胆子抗肿瘤靶点进行了蛋白质-蛋白质相互作用(PPI)网络分析;采用噻唑蓝(MTT)实验测细胞增殖;Western blot检测P53、P21蛋白表达水平;流式细胞术检测细胞周期;AnnexinV-FITC/PI双染法测细胞凋亡。结果:获得鸦胆子有效成分15个;治疗非小细胞肺癌潜在靶点14个;鸦胆子油乳抑制A549、PC-9细胞增殖,呈剂量依赖性(P<0.05);A545、PC-9细胞中P53和P21蛋白表达量升高(P<0.05),细胞周期主要阻滞在G0/G1期(P<0.05);鸦胆子油乳、顺铂处理PC-9细胞,两者联用比单独处理细胞凋亡增加(P<0.05)。结论:鸦胆子能够通过P53调控非小细胞肺癌的增殖活性,并且对化疗药物顺铂具有增敏作用。

Objective:To investigate the effect of Brucea javanica on the proliferation of non-small cell lung cancer cells and the mechanisms.Methods:The effective components of Brucea javanica and their related anti-tumor targets were obtained via network pharmacology analysis.Then the potential targets of Brucea javanica for the treatment of non-small cell lung cancer were established by using GeneCards database.PPI protein network interaction analysis was performed on the anti-tumor targets of Brucea javanica with the help of the String online platform.Cell proliferation was detected by MTT,and P53 and P21 protein were measured by Western blot.Flow cytometry was applied to observing the cell cycle,and AnnexinV-FITC/PI double staining method was used to analyze the cell apoptosis.Results:Fifteen effective components of Brucea javanica were obtained,and 14 potential targets for the treatment of non-small cell lung cancer were established.MTT test showed that Brucea javanica oil emulsion inhibited the proliferation of A549 and PC-9 cells in a dose-dependent(P<0.05).Expression of P53 and P21 protein in A545 and PC-9 cells were up-regulated(P<0.05),and the cell cycle was primarily checked at G0/G1 phase(P<0.05).Treatment of PC-9 cells by Brucea javanica oil emulsion and cisplatin showed that combined use led to more cell apoptosis than single treatment with either of agents(P<0.05).Conclusion:Brucea javanica can not only regulate the proliferation activity of non-small cell lung cancer through P53,but also promote the efficacy of cisplatin.