HIF-1αMMP9 信号通路介导低氧诱导的人视网膜母细胞瘤HXO-RB44细胞侵袭.

Objective: To investigate the effect ofhypoxia on the invasion ability ofretinoblastoma cell and its underlying mechanism. Methods: HXO-RB44 cells were cultured under normoxia (21%O O2) and hypoxia(1%O O2) conditions for 24 hours. The effect of hypoxia on invasion ability of HXO-RB44 cells were monitored with transwell invasion assay; the mRNA and protein expression levels of HIF-1a and MMP9 were detected by RT-PCR and western blot; luciferase assay was performed to assess the HIF-1a regulation by hypoxia, and MMP9 regulation by HIF-1a. Furthermore, HIF-1a and MMP9 siRNA was used to investigate the effect of HIF-1a/MMP9 signaling on hypoxia induced cell invasion. Results: The invaded cell number，mRNA and protein expression of HIF-1a and MMP9 in hypoxia group were higher than those in the normoxia group (P<0.05). The activity of MMP9 in HIF-1a overexpression group was higher than that of the vector group (P<0.05). Compared with the normoxia group，the activity ofHIF-1a in hypoxia group was significantly elevated (P< 0.05). Compared with negative control group，the mRNA and protein expression of HIF-1a and MMP9 in HIF-1a siRNA group were re¬markedly decreased (P<0.05)，whereas the mRNA and protein expression of HIF-1a in MMP9 siRNA group didn't change. The invaded cells in HIF-1a siRNA group and MMP9 siRNA group were significantly decreased (P<0.05). Conclusion: Hypoxia promotes the inva¬sion ofretinoblastoma cell line HXO-RB44 and the activation ofHIF-1a/MMP9 signaling pathway is involved in this process. [ABSTRACT FROM AUTHOR]