HIF-1α与NF-κB通路对胰腺癌缺氧调节及肿瘤进展的作用  

The role of HIF-1α and NF-κB pathways in hypoxia adjustment of pancreatic carcinoma and tumor progression

作　　者：胡恒通[1] 彭波[1] 马清涌[1] 张东[1] 韩亮[1] 张珉[1] 沙焕臣[1] 

机构地区：[1]西安交通大学医学院第一附属医院肝胆外科,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2010年第3期274-278,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

摘　　要：目的观察HIF-1α与NF-κB通路在胰腺癌缺氧调节中的作用,及对下游增殖、侵袭、转移相关因子的影响。方法体外缺氧培养胰腺癌细胞株Mia-PaCa2;分别在0、4、6、8 h时间点用Realti me-PCR和Western blot测定HIF-1α及下游相关因子VEGF、CXCR4、5-LOX和COX-2的表达变化;用RNAi技术干扰HIF-1α,及用PDTC封闭NF-κB的表达,观察它们对胰腺癌细胞缺氧调节及肿瘤进展的作用。结果随缺氧时间推移,HIF-1α及下游相关因子相应上调,其中HIF-1α在mRNA水平的变化无统计学差异,仅在蛋白水平显著上调;当HIF-1α表达被干扰后,其下游相关因子也相应下调,显示了对HIF-1α的依从性;当NF-κB表达被PDTC封闭后,HIF-1α及其下游相关因子呈下调趋势。结论缺氧状态下,胰腺癌细胞通过NF-κB及HIF-1α途径进行自我调节,上调下游相关因子的表达,导致增殖、侵袭、转移力增强。并且NF-κB有可能是HIF-1α的上游调控因素。Objective To observe the role of HIF-1α and NF-κB pathways in hypoxia adjustment of pancreatic carcinoma,as well as their effects on downstream factors related to proliferation,invasion and metastasis.Methods Pancreatic carcinoma cell line Mia-PaCa2 was cultured under hypoxia exposure in vitro.The expression variations of HIF-1α and the downstream-related factors（VEGF,CXCR4,5-LOX and COX-2） were measured by means of realtime-PCR and Western blot at 0h,4h,6h and 8h.RNAi was used to interfere the expression of HIF-1α,and PDTC was used to block NF-κB for observing the role of the two factors in hypoxia adjustment of pancreatic carcinoma and tumor progression.Results As the hypoxia time prolonged,HIF-1α and the downstream-related factors increased accordingly.The expression of HIF-1α had a significant difference at the protein level,but not at the mRNA level.After HIF-1α being interfered,the related factors decreased accordingly,which showed dependence on HIF-1α to some extent.After NF-κB being blocked,HIF-1α and the downstream-related factors declined,too.Conclusion Pancreatic carcinoma cells might make self-adjustment under hypoxia through the NF-κB and HIF-1α pathways to promote the expression of the downstream-related factors,which leads to the proliferation,invasion and metastasis.Besides,NF-κB might be an upstream regulation factor to HIF-1α.

关 键 词：胰腺癌 缺氧诱导因子-1Α NF-ΚB 缺氧 

分 类 号：R735.9[医药卫生—肿瘤]