ERK-VEG FMMP-9信号通路与直肠癌细胞增殖和血管新生的关联

Association of ERK-VEG FMMP-9 Signaling Pathway with Cell Proliferation and Angiogenesis in Esophageal Carcinoma

为了探讨ERK-VEGFMMP-9信号通路与直肠癌细胞增殖和血管新生的关联,本研究以不同浓度(10~100μmol/L)的丙泊酚处理HT-29细胞0、48 h、72 h,研究丙泊酚对HT-29细胞中ERK、MMP-9和VEGF的影响,并利用Western blotting法观察HT-29细胞中ERK1/2、MMP-9和VEGF的表达量与信号通路之间的关系。观察丙泊酚处理后对HT-29细胞增殖能力、血管生成能力、细胞侵袭能力的影响。研究结果表明,在细胞中,VEGF与MMP-9蛋白的表达,均随着丙泊酌剂量的增加而呈现逐渐减少的趋势。与对照组相比,50μmol/L组与100μmol/L组降低(p<0.05);细胞内VEGF和MMP-9蛋白的表达量随药物处理时间的增加而逐渐降低,与0 h相比,48 h组和72h组降低(p<0.05)。细胞中pERK与ERK的比率随着丙泊酌剂量的增加而逐渐降低。与对照组相比,50μmol/L组与100μmol/L组降低(p<0.05),pERK与ERK的比率随着用药时间的增加而逐渐降低。与0相比,48 h组与72 h组降低(p<0.05)。与0剂量相比,丙泊酚加PMA组MMP-9蛋白的表达量显著升高,50μmol/L组和100μmol/L组增加(p<0.05),丙泊酚加PMA组MMP-9蛋白的表达量随着时间的增加而明显的增加,与0h相比,48 h和72 h增加(p<0.05)。与0组相比,丙泊酚加PMA组VEGP的表达量明显增加,50μmol/L组和100μmol/L组增加(p<0.05),丙泊酚加PMA组VEGP的表达量随时间增加而增加,与Oh相比,48h和72h显著增加(p<0.05)。25μmol/L组、50μmol/L组、100μmol/L组Eca109细胞的增殖力、细胞中CAM的新生血管的生成、细胞的侵袭力与对照组相比均显著增加(p<0.05),48 h组、72 h组Eca109细胞的增殖力、细胞中CAM的新生血管的生成、细胞的侵袭力与对照组相比均显著增加(p<0.05)。丙泊酚通过ERK-VEGF/MMP-9的信号的调制,从而抑制人类的HT-29细胞的增殖、侵袭的体外和血管的生成。

To investigate the association between ERK-VEGFMMP-9 signaling pathway and cell proliferation and angiogenesis in esophageal carcinoma,HT-29 cells of human esophageal cancer were cultured and treated with different concentrations(10~100 μmol/L) of propofol for 72 h to observe the effect of propofol on ERK,MMP-9 and VEGF in HT-29 cells.The relationship between ERK1/2,MMP-9 and VEGF signaling pathways in HT-29 cells was observed by western blotting.By observing the effects of propofol on the proliferation capacity,angiogenesis capacity and cell invasion capacity of HT-29 cells,it was founded that the expression of VEGF and MMP-9 proteins in the cells decreased gradually with the increase of the dosage of propofol.Group compared with control group,50 μmol/L and 100 μmol/L group decreased(p<0.05),the expression of MMP-9 protein content gradually reduce with the increase of drug processing time,compared with 0,48 h and 72 h group decreased(p<0.05).The ratio of the cell to ERK decreased with the increase of dose,compared with the control group,the 50 μmol/L group and 100 μmol/L group decreased(p <0.05).The pERK and ERK ratio gradually decreased with the increase of medication time,compared with 0,there was a significant decrease in 48 h group and 72 h group(p<0.0 5).Compared with 0 dose,MMP-9 was increased in the propofol and PMA group,and was increased in the 50 μmol/L group and 100 μmol/L group(p <0.05).MMP-9 increased with time in the propofol and PMA group,and increased at 48 h and 72 h compared with 0(p<0.05).Compared with group 0,VEGP in the propofol and PMA group was increased,50 μmol/L group and 100 μmol/L group were increased(p<0.05).VEGP in propofol and PMA group increased with time,and increased at 48 h and 72 h compared with 0(p<0.05).Compared with control group,25 μmol/L group,50 μmol/L,100 μmol/L group Eca 109 new angiogenesis,cell proliferation,cell CAM cell invasion force were increased(p<0.05).The proliferative capacity of Eca109 cells,the angiogenesis of cell CAM and the invasive power of cells in the 48 h group and the 72 h group were increased compared with the control group(p<0.05).Propofol can inhibit the proliferation,invasion in vitro and angiogenesis of human HT-29 cells through the modulation of ERK-VEGF/MMP-9 signal.