HIF-1α对人脑胶质瘤SHG44细胞恶性度的影响及其机制  

Effect of HIF-1αon malignancy of human glioma SHG44 cells and its possible mechanism

作　　者：陈健 郭志娟 裴美娟 付立华 黄生炫[5] CHEN Jian;GUO Zhijuan;PEI Meijuan;FU Lihua;HUANG Shengxuan(Department of Nerve Trauma Repair,Characteristic Medical Center of Chinese People’s Armed Police Force,Tianjin 300162,China;The Third Medical Genter of Chinese PLA General Hospital,Beijing 100039,China;Department of Neurology,Characteristic Medical Center of Chinese People’s Armed Police Force,Tianjin 300162,China;Military General Medicine Department,Characteristic Medical Center of Chinese People’s Armed Police Force,Tianjin 300162,China;Department of Neurosurgery,Sanming First Hospital Affiliated to Fujian Medical University,Sanming 365000,China)

机构地区：[1]武警特色医学中心神经创伤修复研究所,天津300162 [2]解放军总医院第三医学中心肾内科,北京100039 [3]武警特色医学中心神经内科,天津300162 [4]武警特色医学中心军人全科医学科,天津300162 [5]福建医科大学附属三明市第一医院神经外科,365000

出　　处：《武警医学》2022年第6期484-488,共5页Medical Journal of the Chinese People's Armed Police Force

基　　金：武警后勤部科研项目(CWJ18L004);武警后勤学院基础研究项目(WHJ201721);福建省自然科学基金(2020J011273)

摘　　要：目的探究过表达低氧诱导因子-1α(hypoxia inducible factor 1α,HIF-1α)对人脑胶质瘤SHG44细胞恶性度的影响及其可能机制。方法体外培养SHG44细胞,转染过表达HIF-1α入SHG44细胞,评估HIF-1α转染效率;对比分析HIF-1α过表达对SHG44细胞的增殖、干性、迁移和侵袭的影响;ELISA法检测肿瘤相关炎性反应因子(TNF-α,IL-10,IL-17和IL-1β),Western blot检测SHG44细胞焦亡相关蛋白[炎性小体3(inflammasome3,NLRP3)、凋亡相关斑点样蛋白(apoptosis-associated speck-like protein,ASC)、天冬氨酸蛋白水解酶1(cysteinyl aspartate specific proteinase-1,caspase-1)、GSDMD、GSDME和转化生长因子-β_(1)(transforming growth factor-β_(1),TGF-β_(1))]的表达,明确HIF-1α对焦亡的关系。结果HIF-1α过表达后SHG44细胞明显肿胀增多,细胞的增殖、干性、迁移和侵袭能力较对照组明显增强,与对照组相比肿瘤炎性因子(TNFα,IL-10和IL-1β)表达水平均明显升高,而肿瘤炎性反应抑制因子IL-17表达水平明显下降;HIF-1α过表达后焦亡相关蛋白(NLRP3、ASC、caspase-1、GSDMD、GSDME和TGF-β_(1))表达明显上调(P<0.05)。结论HIF-1α过表达可能通过促进焦亡提高SHG44细胞的增殖、干性、迁移和侵袭能力。Objective To investigate the effect of hypoxia inducible factor-1α(HIF-1α)overexpression on the malignancy of human glioma SHG44 cells and its possible mechanism.Methods Glioma cell SHG44 was cultured in vitro and transfected with HIF-1αoverexpression into SHG44 cells.The effects of HIF-1αoverexpression on the growth and proliferation,cell stem,invasion and metastasis of tumor cells in vitro were analyzed.Finally,the relationship between HIF-1αand pyroptosis were clarified by detecting the expression of HIF-1α,tumor-associated inflammatory factors(TNF-α,IL-10,IL-17 and IL-1β),pyroptosis markers[inflammatory body 3(NLRP3),apoptosis associated speck like protein(ASC),cysteinyl aspartate specific proteinase-1(caspase-1),GSDMD,GSDME and transforming growth factor-β_(1)(TGF-β_(1)nd)].Results MTT,cell cloning,cell scratch and Transwell experiments confirmed that the morphological swelling of SHG44 cells increased significantly after the overexpression of HIF-1α,and cell proliferation and invasion ability were significantly enhanced compared with the control group;ELISA showed that,compared with the control group,tumor inflammatory factor(TNFα,IL-10 and IL-1β)increased significantly,while IL-17 decreased significantly;RT-PCR and Western blot showed that the expression level of HIF-1αin glioma cell line was higher than that in normal brain cells The expression levels of NLRP3,ASC,caspase-1,GSDMD and GSDME inHIF-1αoverexpression group were significantly higher than those in control group(P<0.05).Conclusions The increased expression of HIF-1αin glioma cells SHG44 can increase the proliferation and invasion of glioma cells,which may be achieved by promoting pyroptosis.

关 键 词：低氧诱导因子-1Α 神经胶质细胞 SHG44细胞 焦亡 转染 

分 类 号：R739.41[医药卫生—肿瘤]