發(fā)布時間：2018-03-20 23:27

  本文選題：肺腫瘤　切入點：肺癌細胞A　出處：《中國肺癌雜志》2017年08期 　論文類型：期刊論文

【摘要】：背景與目的綠原酸類物質可通過調節(jié)細胞周期、誘導凋亡、抑制細胞生長等途徑產生抗癌作用,Notch信號通路與人類許多腫瘤都存在密切的關系,本研究旨在探討綠原酸通過Notch1信號通路控制非小細胞肺癌細胞凋亡的作用機制,為臨床應用以及Notch1靶向藥物的研究提供依據。方法 MTT法檢測不同濃度的綠原酸對非小細胞肺癌細胞系A549細胞形態(tài)和細胞增殖的影響;流式細胞儀檢測綠原酸對A549細胞的凋亡和細胞周期的影響;建立A549細胞的裸鼠荷瘤模型;測量腫瘤大小和重量;實時熒光定量PCR法檢測Notch信號通路相關因子的m RNA表達水平;免疫印跡法檢測Notch信號通路相關因子的蛋白表達水平。結果綠原酸抑制A549細胞增殖,誘導A549細胞凋亡,增加細胞G2期/M期細胞百分比增加(P0.05),并且呈現(xiàn)劑量依賴趨勢。在A549細胞的裸鼠荷瘤模型中,實驗組腫瘤大小和體積明顯小于對照組,差異具有統(tǒng)計學意義(P0.01)。試驗組Notch1、VEGF、Delta4、HES1、HEY1 m RNA表達量較對照組明顯減少(P0.05)。實驗組Notch1蛋白明顯減少,PTEN、p-PTEN、p-AKT明顯增加(P0.05)。結論在動物水平,綠原酸可能通過Notch1信號通路調控非小細胞肺癌的凋亡,可能是通過減少VEGF的表達,下調Delta 4水平,從而抑制Notch1信號通路的活化。Notch1信號通路可能通過PTEN與PI3K/AKT通路存在交叉調控作用。
[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.
【作者單位】： 天津中醫(yī)藥大學第一附屬醫(yī)院檢驗科;天津醫(yī)科大學總醫(yī)院腫瘤科;
【分類號】：R734.2

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