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池苗苗,谢长生.南方红豆杉水提物通过PI3K/AKT/mTOR信号通路调控HER2阳性胃癌移植瘤生长实验研究[J].浙江中西医结合杂志,2017,27(1):
南方红豆杉水提物通过PI3K/AKT/mTOR信号通路调控HER2阳性胃癌移植瘤生长实验研究
Mechanism Study of Aqueous extract of Taxus chinensis treat HER2 positive gastric cancer through regulating PI3K/AKT/mTOR signaling pathway
投稿时间:2016-08-13  修订日期:2016-10-28
DOI:
中文关键词:  南方红豆杉,胃癌,PI3K/AKT/mTOR,曲妥珠单抗
英文关键词:
基金项目:浙江省自然科学基金(LY13H290013);浙江省中医药科技计划项目(2013ZA043)
作者单位E-mail
池苗苗 台州市立医院 emma_cmm@126.com 
谢长生* 浙江中医药大学附属第一医院 148140692@qq.com 
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中文摘要:
      目的:初步探讨南方红豆杉水提物抑制磷脂酰肌醇3-激酶(phosphoinositide-3 kinase,PI3K)/蛋白激酶B(protein kinase B,PKB,又称AKT) /雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号通路上相关靶点蛋白调控裸鼠人类表皮生长因子受体2(HER2)阳性胃癌移植瘤生长及其机制。方法:建立荷瘤裸鼠模型,将80只BALB/c裸鼠接种人HER2阳性胃癌NCI-N87细胞株并随机分组给药及取瘤,采用Western blot法检测PI3K、pAKT、mTOR蛋白表达情况,实时荧光定量PCR法检测PI3K、AKT1、mTOR mRNA表达水平。结果 :Western blot法检测PI3K、pAKT、mTOR蛋白,红豆杉中、低剂量组下调PI3K蛋白表达更显著[(0.9123±0.0480、1.1440±0.1663)比1.4160±0.0730,P<0.01],红豆杉各剂量联合赫赛汀后明显下调pAKT蛋白表达(P<0.05),红豆杉组均明显下调mTOR蛋白表达(P<0.01),联合赫赛汀后下调更显著。2、实时荧光定量PCR法检测PI3K、AKT1、mTOR mRNA,红豆杉低剂量组PI3K mRNA表达降低[(0.6906±0.0710)比(0.9018±0.0696),P<0.05],红豆杉各剂量组联合赫赛汀后明显下调AKT1 mRNA表达,红豆杉中、低剂量组mTOR mRNA表达显著降低[(0.8183±0.0664、0.7917±0.0699)比(1.0004±0.1182),P<0.05)]。结论:南方红豆杉水提物可部分下调PI3K、pAKT、mTOR蛋白及PI3K、AKT1、mTOR mRNA表达水平,联合赫赛汀可增强其抑制作用。
英文摘要:
      Objective: Through establish a human epidermal growth factor receptor(HER2) positive gastric cancer xenograft model in BALB/c nude mice, to study the regulation of Aqueous extract of Taxus chinensis(AETC) on PI3K/AKT/mTOR pathway, and to analysis the possible mechanism of action. Methods: The 80 only four to six weeks of BALB/c nude mice were randomized into groups,then giving the corresponding drugs . Mice were killed by cervical dislocation, peel the tissue for inspection. Western Blot was used to detect the PI3K、pAKT、mTOR expression, RT-PCR assay was used to detect PI3K、AKT1、mTOR mRNA expression. Result: 1、The Western Blot method to detect PI3K、pAKT、mTOR protein, medium and low dose groups significantly downregulated the expression of PI3K protein, all dose of AETC combined with Herceptin groups downregulated the expression of pAKT significantly, low、medium dose groups significantly downregulated the expression of mTOR protein. 2、RT-PCR method to detect PI3K、AKT1、mTOR mRNA, expression of PI3K mRNA in low dose groups was downregulated significantly,expression of AKT1 mRNA high, medium dose groups was downregulated significantly, expression of mTOR mRNA in all dose groups was downregulated significantly. Conclusion:1、AETC can down regulate the PI3K/AKT/mTOR signaling pathway, by down regulating the expression of PI3K,pAKT,mTOR expression, the effect is enhanced combined with Herceptin.
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