β-AR信号通路介导去甲肾上腺素提高HT-29细胞侵袭能力的研究  

Effect of Norepinephrine on the Invasiveness of HT-29 Cell Mediated by β-AR Signaling Pathway

作　　者：赵璐 倪依群[1] 尤建良[1] Zhao Lu;Ni Yiqun;You Jianliang(Department of Oncology,Wuxi TCM Hospital Afiliate to Nanjing University of Chinese Medicine,Jiangsu 214071,China)

机构地区：[1]南京中医药大学附属无锡市中医院肿瘤科,214071

出　　处：《医学研究杂志》2020年第11期116-121,共6页Journal of Medical Research

基　　金：江苏省无锡市卫生和计划生育委员会科研项目(Q201704)。

摘　　要：目的探讨去甲肾上腺素通过β-AR信号通路对结肠癌侵袭能力的影响及可能的作用机制。方法以人结肠癌细胞株HT-29为研究对象,采用Transwell观察去甲肾上腺素对HT-29细胞侵袭能力的影响,同时观察加入非选择性β-AR阻断剂普萘洛尔后,HT-29细胞侵袭能力的变化。实时荧光定量PCR和Western blot法检测去甲肾上腺素通过β-AR信号通路对HT-29细胞MMP-2、MMP-9和VEGF的表达及ERK1/2活性的影响。结果0.1、1、10μmol/L去甲肾上腺素组处理后,HT-29细胞的侵袭能力显著高于空白对照组,并且随着去甲肾上腺素浓度的提高,细胞的侵袭能力逐渐增强。而普萘洛尔可逆转去甲肾上腺素对HT-29细胞的促侵袭作用。与空白对照组比较,10μmol/L去甲肾上腺素可显著上调HT-29细胞MMP-2、MMP-9、VEGF mRNA和MMP-2、MMP-9、VEGF、pERK1/2蛋白表达水平。普萘洛尔可拮抗去甲肾上腺素的作用,下调MMP-9和VEGF表达,并减弱去甲肾上腺素对HT-29细胞ERK1/2活性的影响。结论去甲肾上腺素可通过β-AR信号通路提高HT-29细胞的体外侵袭能力。Objective To investigate the effect of norepinephrine on the invasiveness of colon cancer cell line HT-29 and its mechanism mediated byβ-AR signaling pathway.MethodsThe colon cancer cell line HT-29 was used in the research.The cells were divided into control group and norepinephrine group.Transwell invasiveness test was given to examine the changes of invasive ability ofHT-29.The expressions of MMP-2,MMP-9 and VEGF mRNA were measured by quantitative RT-PCR.The levels of MMP-2,MMP-9,VEGF,and ERK1/2 proteins were measured by Western blot.ResultsNorepinephrine dose-dependently enhanced the invasion ability of HT-29 cells,which could be inhibited by propranolol hydrochloride.Norepinephrine could up-regulated the mRNA and protein expressions of MMP-2,MMP-9 and VEGF in HT-29 cells,as well as activated ERK1/2 signaling pathway.Propranolol hydrochloride could reverse the effects of norepinephrine on HT-29 cells.ConclusionNorepinephrine can promote the invasiveness of HT-29 viaβ-ARsignaling pathway.

关 键 词：结肠癌 去甲肾上腺素 β-AR信号通路 细胞侵袭 

分 类 号：R73[医药卫生—肿瘤]