HIF-1α与NF-κB通路对胰腺癌缺氧调节及肿瘤进展的作用

Objective To observe the role of HIF-1α and NF-kB 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-kB 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-kB being blocked, HIF-1α and the downstream-related factors declined, too. Conclusion Pancreatic carcinoma cells might make self-adjustment under hypoxia through the NF-kB and HIF-1α pathways to promote the expression of the downstream-related factors, which leads to the proliferation, invasion and metastasis. Besides, NF-kB might be an upstream regulation factor to HIF-1α.