【摘要】 目的 观察HIF1α与NFκB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MiaPaCa2;分别在0、4、6、8h时间点用RealtimePCR和Western blot测定HIF1α及下游相关因子VEGF、CXCR4、5LOX和COX2的表达变化;用RNAi技术干扰HIF1α，及用PDTC封闭NFκB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，HIF1α及下游相关因子相应上调，其中HIF1α在mRNA水平的变化无统计学差异，仅在蛋白水平显著上调;当HIF1α表达被干扰后，其下游相关因子也相应下调，显示了对HIF1α的依从性;当NFκB表达被PDTC封闭后，HIF1α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NFκB及HIF1α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NFκB有可能是HIF1α的上游调控因素。
【关键词】 胰腺癌;缺氧诱导因子1α;NFκB;缺氧
The role of HIF1α and NFκB pathways in hypoxia adjustment of
pancreatic carcinoma and tumor progressionHU Hengtong, PENG Bo, MA Qingyong, ZHANG Dong,
HAN Liang, ZHANG Min, SHA Huanchen
(Department of Hepatobiliary Surgery, the First Affiliated Hospital,
Medical School of Xian Jiaotong University, Xian 710061, China)ABSTRACT: Objective To observe the role of HIF1α and NFκB 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 MiaPaCa2 was cultured under hypoxia exposure in vitro. The expression variations of HIF1α and the downstreamrelated factors (VEGF, CXCR4, 5LOX and COX2) were measured by means of realtimePCR and Western blot at 0h, 4h, 6h and 8h. RNAi was used to interfere the expression of HIF1α, and PDTC was used to block NFκB for observing the role of the two factors in hypoxia adjustment of pancreatic carcinoma and tumor progression. Results As the hypoxia time prolonged, HIF1α and the downstreamrelated factors increased accordingly. The expression of HIF1α had a significant difference at the protein level, but not at the mRNA level. After HIF1α being interfered, the related factors decreased accordingly, which showed dependence on HIF1α to some extent. After NFκB being blocked, HIF1α and the downstreamrelated factors declined, too. Conclusion Panc
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