动物水平的绿原酸通过Notch1信号通路调控非小细胞肺癌凋亡及机制研究

发布时间：2018-03-20 23:27

本文选题：肺肿瘤　切入点：肺癌细胞A　出处：《中国肺癌杂志》2017年08期 　论文类型：期刊论文

【摘要】：背景与目的绿原酸类物质可通过调节细胞周期、诱导凋亡、抑制细胞生长等途径产生抗癌作用,Notch信号通路与人类许多肿瘤都存在密切的关系,本研究旨在探讨绿原酸通过Notch1信号通路控制非小细胞肺癌细胞凋亡的作用机制,为临床应用以及Notch1靶向药物的研究提供依据。方法 MTT法检测不同浓度的绿原酸对非小细胞肺癌细胞系A549细胞形态和细胞增殖的影响;流式细胞仪检测绿原酸对A549细胞的凋亡和细胞周期的影响;建立A549细胞的裸鼠荷瘤模型;测量肿瘤大小和重量;实时荧光定量PCR法检测Notch信号通路相关因子的m RNA表达水平;免疫印迹法检测Notch信号通路相关因子的蛋白表达水平。结果绿原酸抑制A549细胞增殖,诱导A549细胞凋亡,增加细胞G2期/M期细胞百分比增加(P0.05),并且呈现剂量依赖趋势。在A549细胞的裸鼠荷瘤模型中,实验组肿瘤大小和体积明显小于对照组,差异具有统计学意义(P0.01)。试验组Notch1、VEGF、Delta4、HES1、HEY1 m RNA表达量较对照组明显减少(P0.05)。实验组Notch1蛋白明显减少,PTEN、p-PTEN、p-AKT明显增加(P0.05)。结论在动物水平,绿原酸可能通过Notch1信号通路调控非小细胞肺癌的凋亡,可能是通过减少VEGF的表达,下调Delta 4水平,从而抑制Notch1信号通路的活化。Notch1信号通路可能通过PTEN与PI3K/AKT通路存在交叉调控作用。
[Abstract]:Background and objective Lv Yuan acids can produce anticancer effects by regulating cell cycle, inducing apoptosis and inhibiting cell growth. The Notch signaling pathway is closely related to many human tumors. The aim of this study was to investigate the mechanism of Lv Yuan controlling apoptosis of non-small cell lung cancer cells through Notch1 signaling pathway. Methods the effects of different concentrations of Lv Yuan on the morphology and proliferation of non-small cell lung cancer cell line A549 were detected by MTT assay. Flow cytometry was used to detect the effect of Lv Yuan on the apoptosis and cell cycle of A549 cells. The tumor-bearing model of A549 cells was established. The tumor size and weight were measured. The expression of m RNA related to Notch signaling pathway was detected by real-time fluorescence quantitative PCR. Results Lv Yuan inhibited the proliferation of A549 cells and induced apoptosis of A549 cells. In A549 cell model, the tumor size and volume in the experimental group were significantly smaller than those in the control group. The difference was statistically significant (P 0.01). The expression of Notch1 VEGF4 HES1HEY1 m RNA in the experimental group was significantly lower than that in the control group (P 0.05). The Notch1 protein in the experimental group significantly decreased PTENU p-PTENN p-AKT increased significantly. Conclusion at the animal level, Lv Yuan may regulate the apoptosis of non-small cell lung cancer through Notch1 signaling pathway. It may be that by reducing the expression of VEGF and down-regulating the level of Delta _ 4, the activation of Notch1 signaling pathway. Notch1 signaling pathway may have cross-regulation by PTEN and PI3K/AKT pathway.
【作者单位】：天津中医药大学第一附属医院检验科;天津医科大学总医院肿瘤科;
【分类号】：R734.2

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