PI3K／AKT及MEK／ERK信号通路在肿瘤血管内皮细胞迁移中的作用

目的：研究磷脂酰肌醇3激酶（PI3K）／丝氨酸苏氨酸蛋白激酶（AKT）及丝裂原细胞外信号调节激酶（MEK）／细胞外信号调节激酶（ERK）信号通路在肿瘤血管内皮细胞迁移中的作用及机制。方法用不同浓度的PI3K／AKT信号通路抑制剂LY294002（2．50、7．50、15．00μmol／L）；MEK／ERK信号通路抑制剂PD98059（2．50、7．50、15．00μmol／L）分别处理肿瘤血管内皮细胞，以DMEM‐F12培养基，加入0．10％二甲基亚砜（DMSO）的培养基分别作为对照，通过细胞划痕试验，定向迁移试验和Transwell试验来检测不同的信号通路抑制剂对肿瘤血管内皮细胞的水平、垂直和定向迁移能力的影响。结果0．1％DMSO对内皮细胞的迁移无明显影响，其作用后内皮细胞的迁移能力与DMEM‐F12单独作用无明显区别，说明小剂量DMSO作为LY294002、PD98059的溶剂不影响肿瘤血管内皮细胞的迁移功能；应用信号通路抑制剂LY294002、PD98059处理后，内皮细胞迁移能力受抑制，且随着抑制剂浓度增高而增大；LY294002与PD98059组比较，前者迁移距离更小，细胞迁移数较后者少，二者比较差异有统计学意义（P＜0．05）。结论抑制PI3K／AKT和MEK／ERK信号通路均能抑制肿瘤血管内皮细胞的水平、垂直和定向迁移，且与抑制剂浓度呈正相关；PI3K／AKT信号通路对内皮细胞迁移的影响比MEK／ERK信号通路明显。

Role of PI3K/AKT and MEK/ERK signaling pathway in tumor vascular endothelial cell migration

Objective To research the effect and mechanism of phosphatidylinositol 3‐kinase(PI3K)/serine threonine protein kinase(AKT) and mitogen extracellular signal‐regulated kinase(MEK)/extracellular signal‐regulated kinase(ERK) signaling path‐way in tumor vascular endothelial cell migration .Methods The different concentrations of PI3K/AKT signaling pathway inhibitor LY294002 (2 .50 ,7 .50 ,15 .00 μmol/L) and the MEK/ERK signaling pathway inhibitor PD98059 (2 .50 ,7 .50 ,15 .00 μmol/L) were used to treat the tumor‐derived endothelial cells respectively .The DMEM‐F12 culture medium was added into 0 .10% DMSO culture medium as the control .The cell scratch test ,cell directional migration test and Transwell test were adopted to detect the effects of different signaling pathway inhibitors on the tumor vascular endothelial cells level ,horizontal ,vertical and directional mi‐gration .Results 0 .10% DMSO had no significant effect on endothelial cell migration and the role of endothelial cells′migration a‐bility after its action had no obvious difference compared with the single DMEM‐F12 medium action ,indicating that small doses of DMSO as the solvent of LY294002 ,PD98059 did not affect the tumor vascular endothelial cell migration function ;after treatment by signaling pathway inhibitor LY294002 and PD98059 ,the endothelial cell migration ability was suppressed and increased with the in‐hibitor concentration increase ;compared with the PD98059 group ,the migration distance in the LY294002 group was smaller and the number of migrating cells was less ,the differences had statistical significance (P<0 .05) .Conclusion The inhibition of PI3K/AKT and MEK/ERK signaling pathway can inhibit the level of tumor vascular endothelial cells ,vertical and directional migration , and which is positively correlated with the concentration of inhibitor ;the effect of PI3K/AKT signal pathway on the migration of endothelial cells is more significant than that of the MEK/ERK signal pathway .