【摘要】 目的:探讨脂氧素A4(LXA4)对肝细胞生长因子(HGF)诱导的HepG2肝癌细胞血管生成相关细胞因子表达的影响。方法:体外培养HepG2肝癌细胞,实验分为空白组、HGF处理组、HGF+LXA4处理组、HGF+脂氧素受体激动剂BML-111处理组。RT-PCR检测脂氧素受体(ALX)表达情况,Western blotting检测COX-2、MMP-2、MMP-9、IκBα和NF-κB p65的表达量,ELISA检测TNF-α、IL-1β、VEGF和TGF-β分泌水平,荧光素酶报告质粒检测NF-κB转录活性。结果:HepG2肝癌细胞表达ALX,LXA4和BML-111下调COX-2、MMP-2和MMP-9,抑制TNF-α、IL-1β、VEGF和TGF-β分泌,并且干扰NF-κB转位及其转录活性。结论:脂氧素抑制HGF诱导HepG2肝癌细胞表达血管生成相关细胞因子,包括VEGF、COX-2、TNF-α、IL-1β、TGF-β、MMP-2及MMP-9,此效应可能通过干扰NF-κB活化实现。更多还原

【Abstract】 AIM: To explore the possibility that lipoxin A4(LXA4) regulates the expression of angiogenesis-related cytokines in HepG2 cells induced by hepatocyte growth factor(HGF).METHODS: The HepG2 cells were divided into control group,HGF treatment group,HGF+LXA4 treatment group and HGF+BML-111(an agonist of lipoxin A4 receptor) treatment group.The expression of lipoxin A4 receptor in HepG2 cells was measured by RT-PCR.The protein levels of COX-2,MMP-2,MMP-9,IκBα and NF-κB p65 in the cells were determined by Western blotting.The release of TNF-α,IL-1β,VEGF and TGF-β in the supernatants of the cell culture was examined by ELISA.The activity of NF-κB transcription in HepG2 cells was tested by transfection and luciferase activity assay.RESULTS: The expression of lipoxin A4 receptor was detected in HepG2 cells.LXA4 and BML-111 were able to down-regulate HGF-induced production of COX-2,MMP-2 and MMP-9.The secretion of TNF-α,IL-1β,VEGF and TGF-β was also decreased.Furthermore,LXA4 and BML-111 restrained HGF-induced IκBα degradation,NF-κB translocation,and the transcriptional activity of NF-κB in HepG2 cells.CONCLUSION: LXA4 is able to inhibit HGF-induced angiogenesis-related cytokines,including VEGF,COX-2,TNF-α,IL-1β,TGF-β,MMP-2 and MMP-9,by inhibition of NF-κB activation.更多还原