肺癌患者HIF-1α过表达及其靶向干预对VEGF的调控作用  

Over-expressions of HIF-1αand its target-regulating role on VEGF in lung cancer

作　　者：时杨[1,2] 赛文莉[2] 黄海涛[3] 吴广洲[1] 姚登福[1] SHI Yang;SAI Wenli;HUANG Haitao;WU Guangzhou;YAO Dengfu(Department of Thoracic Surgery,4th Affiliated Hospital of Nantong University,Yancheng 224001;Research Center of Clinical Medicine,the Affiliated Hospital of Nantong University;Department of Thoracic Surgery,the Second Affiliated Hospital of Nantong University)

机构地区：[1]南通大学第四附属医院胸外科,盐城224001 [2]南通大学附属医院临床医学研究中心 [3]南通大学第二附属医院胸外科

出　　处：《南通大学学报（医学版）》2021年第4期297-301,F0002,共6页Journal of Nantong University(Medical sciences)

基　　金：中国博士后基金资助项目(2018M632352);南通市科技计划项目(MS12019016,MS12020021)。

摘　　要：目的:分析肺癌患者缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)的表达情况及其对血管内皮生长因子(vascular endothelial growth factor,VEGF)的调控作用。方法:收集住院肺腺癌患者(n=60)术后新鲜癌和自身配对非癌组织制作组织芯片,以免疫组织化学法分析HIF-1α和VEGF的表达与胞内定位;构建并筛选HIF-1αmRNA短发夹RNA干扰质粒转染肺癌A549细胞,观察对VEGF表达,癌细胞增殖、侵袭及迁移等生物学特性的影响。结果:肺癌组织中HIF-1α和VEGF呈棕黄色,颗粒状过表达状态,定位于胞质和胞核,两者在肺癌组中的表达均显著高于非癌组(均P<0.001);两者表达水平与肺癌TNM分期、分化程度、淋巴结转移或远处转移显著相关(P<0.05)。将特异的短发夹RNA干扰质粒转染肺癌A549细胞后,癌细胞增殖显著受抑,呈时间依赖性;转染72 h时HIF-1αmRNA抑制率为87.1%(P<0.001),VEGF抑制率为54.3%(P<0.001),并显著抑制癌细胞迁移(P<0.001)和侵袭(P<0.001)能力。结论:肺癌HIF-1α和VEGF过表达,靶向HIF-1α转录显著抑制VEGF表达及相关生物学行为。Objective:To investigate the expression of hypoxia-inducible factor-1α(HIF-1α)and its regulation of vascular endothelial growth factor(VEGF)in lung cancer.Methods:The cancerous and their self-control noncancerous tissues of lung adenocarcinoma(n=60)were collected,and the expression and cellular localization of HIF-1αand VEGF were analyzed by tissue microarray with immunohistochemistry.The construction and screening of HIF-1 mRNA short hairpin RNA interfering plasmids were transfected into A549 cells to observe the effect of VEGF and the biological characteristics of the cell proliferation,invasion and migration.Results:The HIF-1αor VEGF positive material consisted of buffy fine particles mainly localized in cytoplasm and nucleus;the incidences of HIF-1αor VEGF expression in lung cancerous group was significantly higher(P<0.001)than that in their non-cancerous group.The expressions of HIF-1αand VEGF were significantly correlated with tumor TNM stage,differentiation degree,lymph node or distal metastasis of lung cancer(P<0.05).The A549 cell proliferation was significantly inhibited after the specific plasmids transfection at 72 h,and the inhibition rates were 87.1%in HIF-1α(P<0.001)and 54.3%in VEGF(P<0.001)with significantly decreasing of the cancerous cell migration(P<0.001)and invasion(P<0.001).Conclusion:The overexpressions of HIF-1αand VEGF in lung cancer,targeting HIF-1αtranscription could significantly inhibit the expression of VEGF and related biological behavior.

关 键 词：肺癌 缺氧诱导因子-1Α 血管内皮生长因子 组织芯片 靶向抑制 

分 类 号：R734.2[医药卫生—肿瘤]