VEGF促进肝癌SMMC-7721细胞侵袭性的自分泌机制

Vascular endothelial growth factor promotes the invasion of human hepatocellular carcinoma SMMC-7721 cells via an autocrine mechanism

目的:探讨促血管内皮生长因子(VEGF)对人肝癌细胞SMMC-7721侵袭力以及对该细胞中基质金属蛋白酶9(MMP-9)的影响,初步研究VEGF对肿瘤侵袭和转移的影响及可能的作用机制.方法:使用VEGF体外培养人肝癌SMMC-7721细胞,通过细胞体外侵袭实验检测细胞侵袭能力的改变,再分别使用30μg/L、10μg/LVEGF培养人肝癌SMMC-7721细胞,以正常培养人肝癌SMMC-7721细胞为空白对照组.使用半定量RT-PCR和Western blot法对3组细胞中MMP-9的 mRNA和蛋白表达水平进行分析.结果:细胞体外侵袭实验显示,外加VEGF培养后,细胞侵袭力明显增强(P<0.01);MMP-9 mRNA和蛋白的表达在外加VEGF组中要明显高于空白对照组(0.479±0.025,0.665±0.024vs0.315±0.022;0.521±0.026,0.662±0.026vs0.366±0.025,均P<0.01),且高浓度和低浓度组之间也有明显差别.结论:肝癌SMMC-7721细胞系中存在有自分泌机制,VEGF可通过自分泌机制上调肝癌细胞的MMP-9表达,进而促进肿瘤的浸润转移.

AIM： To evaluate the effects of vascular endothelial growth factor （VEGF） on cell invasion and matrix metalloprotease-9 （MMP-9） expression in human hepatocellular carcinoma cell line SMMC-7721. METHODS： SMMC-7721 cells were incubated with different concentrations of VEGF. The invasive capacity of cells was determined using cell invasion assay. The expression of MMP-9 mRNA and protein was detected by reverse transcription-polymerase chain reaction （RTPCR） and Western blot, respectively. RESULTS： Compared with normal control cells, cells treated with VEGF had signifi cantly increased invasive capacity （P 〈 0.01）. The expression levels of MMP-9 mRNA and protein in VEGF-treated cells were signifi cantly higher than those in normal control cells （0.479 ± 0.025, 0.665 ± 0.024 vs 0.315 ± 0.022; 0.521 ± 0.026, 0.662 ± 0.026 vs 0.366 ± 0.025, both P 〈 0.01）. The ex-pression levels of MMP-9 mRNA and protein in cells incubated with high-concentration VEGF （30 μg/L） were signif icantly higher than those in cells incubated with low-concentration VEGF （10 μg/L） （P 〈 0.01）. CONCLUSION： VEGF can upregulate MMP-9 expression and promote cell invasion in human hepatocellular carcinoma SMMC-7721 cells via an autocrine mechanism.