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贞芪扶正颗粒调控PTEN/PI3K/AKT信号通路影响肺癌A549细胞的增殖与凋亡    

Zhenqi Fuzheng(贞芪扶正)Granules Affect the Proliferation and Apoptosis of A549 Cells by Regulating the PTEN/PI3K/AKT Signaling Pathway

文献类型:期刊文献

中文题名:贞芪扶正颗粒调控PTEN/PI3K/AKT信号通路影响肺癌A549细胞的增殖与凋亡

英文题名:Zhenqi Fuzheng(贞芪扶正)Granules Affect the Proliferation and Apoptosis of A549 Cells by Regulating the PTEN/PI3K/AKT Signaling Pathway

作者:徐倩娟[1,2];段海婧[1,2];宁艳梅[1,2];杜丽东[1,2];吴国泰[1,2];任远[1,2]

第一作者:徐倩娟

机构:[1]甘肃中医药大学药学院,兰州730000;[2]甘肃省中药药理与毒理学重点实验室,兰州730000

第一机构:甘肃中医药大学药学院(西北中藏药协同创新中心办公室)

年份:2022

卷号:38

期号:5

起止页码:57

中文期刊名:中药药理与临床

外文期刊名:Pharmacology and Clinics of Chinese Materia Medica

收录:北大核心:【北大核心2020】;CSCD:【CSCD2021_2022】;

基金:甘肃省中药药理与毒理学重点实验室开放基金项目(编号:GSZYYL-2019-KF-003)。

语种:中文

中文关键词:贞芪扶正颗粒;人第10号染色体缺失的磷酸酶/磷脂酰肌醇三激酶/蛋白激酶通路;A549细胞;增殖;凋亡

外文关键词:Zhenqi Fuzheng Granules;PTEN/PI3K/AKT signaling pathway;A549 cells;Proliferation;Apoptosis

摘要:目的:研究贞芪扶正颗粒对肺癌A549细胞增殖与凋亡的影响及作用机制。方法:建立肺癌A549细胞体外培养模型,用贞芪扶正颗粒含药血清干预,采用MTT法和流式细胞术观察贞芪扶正颗粒含药血清对A549细胞增殖、凋亡及细胞周期的影响;基于网络药理学分析贞芪扶正颗粒的作用靶点,运用Western blot技术检测贞芪扶正颗粒对PTEN、PI3K、AKT蛋白表达的影响。结果:网络药理研究显示,贞芪扶正颗粒活性成分治疗肺癌Degree排名靠前的靶点为TP53、ESR1、AKT1、CASP3、MYC、PTEN、等,KEGG主要富集在癌症通路、癌症蛋白多糖通路、癌症micro-RNA通路、PI3K-AKT信号通路、等。与空白对照组比较,贞芪扶正颗粒10%、20%含药血清组A549细胞存活率显著下降(P<0.01),A549细胞凋亡率显著增加(P<0.01),G_(0)/G_(1)期细胞浓度分数显著升高(P<0.01),S期和G2/M期细胞浓度分数明显降低(P<0.05或P<0.01),G2/M期细胞浓度分数显著降低(P<0.01),PTEN蛋白表达明显上调(P<0.05或P<0.01),Pi3k、Akt mRNA和蛋白表达显著下调(P<0.01)。结论:贞芪扶正颗粒可将A549细胞阻滞于G_(0)/G_(1)期,使细胞不能进入S期进行DNA的合成,进而抑制A549细胞的增殖,诱导A549细胞的凋亡;上调PTEN的表达、抑制PI3K/AKT信号通路可能是贞芪扶正颗粒抑制A549细胞增殖的重要机制。
Objective:To analyze the effect and mechanism of Zhenqi Fuzheng Granules on the proliferation and apoptosis of A549 cells.Methods:The lung cancer A549 cell model in vitro was established and then intervened by drug-containing serum of Zhenqi Fuzheng Granules.MTT and flow cytometry were used to observe the effects of drug-containing serum of Zhenqi Fuzheng Granules on the proliferation,apoptosis,and cell cycle of A549 cells.The action targets of Zhenqi Fuzheng Granules were analyzed by network pharmacology.Western blot was used to detect the effect of Zhenqi Fuzheng Granules on the protein expression of PTEN,PI3 K,and AKT.Results:The network pharmacology results showed that in terms of Degree,the top targets of Zhenqi Fuzheng Granules in treating lung cancer included TP53,ESR1,AKT1,CASP3,MYC,and PTEN.KEGG enrichment pathways were mainly cancer pathway,cancer protein polysaccharide pathway,cancer mRNA pathway,PI3 K-AKT signaling pathway,etc.Compared with the blank control group,the Zhenqi Fuzheng Granules groups(10%and 20%drug-containing serum)showed decreased survival rate(P<0.01),increased apoptosis rate of A549 cells(P<0.01),increased proportions of cells in the G0/G1 phase(P<0.01),decreased proportion of cells in the S phase and G2/M phase(P<0.05 or P<0.01),up-regulated PTEN protein expression(P<0.05 or P<0.01),and down regulated protein and mRNA expression of PI3 K and AKT(P<0.01).Conclusion:Zhenqi Fuzheng Granules can block A549 cells in the G0/G1 phase and prevent cells from entering S phase for DNA synthesis,thus inhibiting the proliferation and inducing apoptosis of A549 cells.The key mechanism of Zhenqi Fuzheng Granules in inhibiting the proliferation of A549 cells may be associated with the up-regulation of PTEN expression and inhibition of the PI3 K/AKT signaling pathway.

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