| 池苗苗,王亚坤,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,2019,29(3): |
| 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：2018-10-10 修订日期：2019-01-21 |
| 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:T.chinensis var, trastuzumab,gastric cancer, PI3K/AKT/mTOR, trastuzumab |
| 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); 萧山区重大科技攻关项目(2016208) |
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| 中文摘要: |
| 目的:初步探讨南方红豆杉水提物抑制PI3K/AKT信号通路上相关靶点蛋白调控裸鼠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（0.9401±0.0521、0.7899±0.0711、0.8313±0.0414、0.7219±0.0100）比（1.1988±0.2667），P<0.05，红豆杉高、低剂量下调mTOR蛋白表达（1.0219±0.1769、1.018±0.129）比（1.3349±0.2045），P<0.05，联合赫赛汀后下调明显（0.7236±0.1709、0.8217±0.1262、0.822±0.0809）比（1.3349±0.2045），P<0.01。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（0.6337±0.2248、0.5666±0.1758、0.7192±0.1219）比（1.002±0.0773），P<0.01，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 HER2 positive gastric cancer xenograft model in BALB/c nude mice, to study the regulation of Aqueous extract of Taxus chinensis 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(0.9123±0.0480、1.1440±0.1663 vs (1.4160±0.0730), P<0.01, all dose of AETC combined with Herceptin groups?downregulated?the expression of pAKT significantly(0.9401±0.0521、0.7899±0.0711、0.8313±0.0414、0.7219±0.0100) vs (1.1988±0.2667), P<0.05, low、medium dose groups significantly?downregulated the expression of mTOR protein(1.0219±0.1769、1.018±0.129) vs (1.3349±0.2045), P<0.05,all dose of AETC combined with Herceptin groups?downregulated?the expression of mTOR significantly(0.7236±0.1709、0.8217±0.1262、0.822±0.0809) vs(1.3349±0.2045)，P<0.01. 2、RT-PCR method to detect PI3K、AKT1、mTOR mRNA, expression of PI3K mRNA in low dose groups was downregulated?significantly(0.6906±0.0710) vs(0.9018±0.0696)，P<0.05,expression of AKT1 mRNA high, medium dose groups was downregulated?significantly, (0.6337±0.2248、0.5666±0.1758、0.7192±0.1219) vs (1.002±0.0773)，P<0.01,expression of mTOR mRNA in low、 medium dose groups was downregulated?significantly, (0.8183±0.0664、0.7917±0.0699)vs (1.0004±0.1182),P<0.05. 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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