胃癌细胞中Caveolin-1对表皮生长因子受体2活化的影响

Effect of Caveolin-1 on activation of epidermal growth factor receptor 2 in gastric cancer cells

目的:检测Caveolin-1蛋白(Cav-1)对胃癌(gastric cancer,GC)细胞株NCI-N87恶性生物学行为的影响及其可能的作用机制。方法:构建Cav-1过表达稳转染细胞系N87/Cav-1,应用MTT、克隆形成、划痕修复实验检测Cav-1对胃癌细胞株NCI-N87恶性生物学行为的影响,应用Western blotting检测在EGF配体诱导下Cav-1蛋白对Her-2活化及ERK、Akt信号通路的影响。结果:Cav-1过表达可明显抑制胃癌细胞NCI-N87的增殖及迁移能力;在配体EGF刺激下,Cav-1过表达明显抑制了Her-2酪氨酸磷酸化水平以及P-ERK/ERK、P-AKT/AKT的比率(P<0.01)。结论:Cav-1过表达可明显抑制EGF诱导的Her-2酪氨酸磷酸化水平,并可能通过下游MAPK及PI3K/Akt信号通路的作用抑制了胃癌细胞株NCI-N87的增殖及迁移能力。

Objective:To investigate the effect of Caveolin-l(Cav-1)protein on the malignant biological behaviors of NCI-N87gastric cancer cells,and further to analyze the possible molecular mechanisms.Methods:NCI-N87cell line that stably expressing Car-1was constructed;MTT assay,colony formation assay and wound healing assay were used to examine the effect of Cav-1on the malignant bi- ological behaviors of gastric cancer cells;Western bloting was used to detect the effect of Car-1 protein on Her-2 activation as well as the ERK and Akt signaling pathway under the induction with EGF ligand.Results:Over-expression of Cav-1significantly inhibited the proliferation and migration of NCI-N87 cells.With the stimulation of EGF ligand,Cav-1 over-expression significantly inhibited the tyrosine phosphorylation level of Her-2 and the ratio of P-ERK/ERK as well as P-AKT/AKT.Conclusion:The over-expression of Cav-1 could significantly inhibit Her-2 tyrosine phosphorylation,and may inhibit the proliferation and migration of NCI-N87 cells via the down-stream MAPK and PI3K/Akt signaling pathway.