缺氧通过上调 HIF-1α/MMP9 信号通路促进视网膜母细胞瘤细胞的体外侵袭。
Hypoxia promotes invasion of retinoblastoma cells in vitro by upregulating HIF-1α/MMP9 signaling pathway.
机构信息
Department of Ophthalmology, Chengdu University of Traditional Chinese Medicine, Sichuan Chengdu, China.
出版信息
Eur Rev Med Pharmacol Sci. 2017 Dec;21(23):5361-5369. doi: 10.26355/eurrev_201712_13921.
OBJECTIVE
The aim of this study is to investigate the effect of hypoxia-inducible transcription factors-1α (HIF-1α)/matrix metalloproteinase 9 (MMP9) signaling pathway on hypoxia triggered invasion in retinoblastoma cell line HXO-RB44.
MATERIALS AND METHODS
HXO-RB44 cells were cultured under hypoxia conditions for 24 h. The effect of hypoxia on invasion ability of HXO-RB44 cells was monitored with transwell invasion assay; the mRNA and protein expression levels of HIF-1α and MMP9 were detected by Real-time polymerase chain reaction (RT-PCR) and Western blot; luciferase assay was performed to assess the MMP9 regulation by HIF-1α, and HIF-1α regulation by hypoxia. Furthermore, HIF-1α and MMP9 siRNA were used to investigate the effect of HIF-1α/MMP9 signaling on hypoxia-induced cell invasion.
RESULTS
The results demonstrated that hypoxia could promote HXO-RB44 cells invasion. The mRNA and protein level of HIF-1α and MMP9 were upregulated by hypoxia treatment, whereas HIF-1α and MMP9 siRNA could reverse these processes.
CONCLUSIONS
Hypoxia promotes retinoblastoma cell line HXO-RB44 invasion by activating HIF-1α/MMP9 signaling pathway.
目的
本研究旨在探讨低氧诱导转录因子-1α（HIF-1α）/基质金属蛋白酶 9（MMP9）信号通路对人视网膜母细胞瘤细胞系 HXO-RB44 缺氧诱导侵袭的影响。
材料与方法
将 HXO-RB44 细胞在缺氧条件下培养 24 小时。通过 Transwell 侵袭实验监测缺氧对 HXO-RB44 细胞侵袭能力的影响；实时聚合酶链反应（RT-PCR）和 Western blot 检测 HIF-1α 和 MMP9 的 mRNA 和蛋白表达水平；通过荧光素酶实验评估 HIF-1α 对 MMP9 的调控作用以及缺氧对 HIF-1α 的调控作用。此外，采用 HIF-1α 和 MMP9 siRNA 研究 HIF-1α/MMP9 信号通路对缺氧诱导细胞侵袭的影响。
结果
结果表明，缺氧可促进 HXO-RB44 细胞侵袭。缺氧处理可上调 HIF-1α 和 MMP9 的 mRNA 和蛋白水平，而 HIF-1α 和 MMP9 siRNA 可逆转这些过程。
结论
缺氧通过激活 HIF-1α/MMP9 信号通路促进人视网膜母细胞瘤细胞系 HXO-RB44 的侵袭。
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