p38MAPK信号通路在TLR4促进胰腺癌血管生成中的作用

发布时间：2019-01-23 20:38

【摘要】：目的探讨Toll样受体-4(TLR4)和p38丝裂原活化蛋白激酶(p38 MAPK)信号通路在胰腺癌血管生成中的作用。方法以脂多糖(LPS)、TLR4-siRNA及p38 MAPK信号通路阻断剂SB203580分别作用于体外培养的胰腺癌PANC-1细胞,Western blot检测TLR4、血管内皮生长因子(VEGF)、磷酸化p38丝裂原活化蛋白激酶(p-p38)蛋白表达。收集各种因素处理后的PANC-1细胞培养液,观察其对人脐静脉内皮细胞(HUVECs)增殖、迁移和管腔形成的影响。结果 LPS组的HUVECs增殖率、迁移数目和管腔形成个数分别为(139.2±12.6)%、48.1±9.1和47.8±9.6,均显著高于对照组(P0.05)。TLR4-siRNA组的HUVECs增殖率、迁移数目和管腔形成个数分别为(60.2±8.7)%、31.3±4.5和17.2±3.3,均显著低于对照组(P0.01);SB203580组的HUVECs增殖率[(79.6±8.9)%]、迁移数目(21.6±4.3)和管腔形成个数(23.5±4.3)均较对照组显著减少(P0.05);且TLR4-siRNA+LPS、B203580+LPS组的HUVECs增殖率、迁移数目和管腔形成个数均分别显著低于LPS组(P0.01)。与对照组相比,LPS组VEGF、p-p38蛋白表达均明显增加,TLR4-siRNA组、SB203580组TLR4、VEGF、p-p38蛋白表达明显减少;且TLR4-siRNA+LPS组、SB203580+LPS组VEGF、p-p38表达较LPS组明显减少。结论 TLR4可促进胰腺癌的血管生成,其机制与激活p38 MAPK信号通路、促进VEGF表达有关。
[Abstract]:Objective to investigate the role of Toll like receptor 4 (TLR4) and p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway in angiogenesis of pancreatic cancer. Methods TLR4, vascular endothelial growth factor (VEGF), was detected in PANC-1 cells of pancreatic cancer treated with lipopolysaccharide (LPS), TLR4-siRNA) and p38 MAPK signal pathway blocker (SB203580) in vitro. Phosphorylated p38 mitogen-activated protein kinase (p-p38) protein was expressed. The effects of various factors on (HUVECs) proliferation, migration and lumen formation of human umbilical vein endothelial cells (HUVEC) were observed. Results the proliferation rate of HUVECs, the number of migration and the number of lumen formation in LPS group were (139.2 卤12.6)%, 48.1 卤9.1 and 47.8 卤9.6, respectively, which were significantly higher than those in control group (P0.05). The number of migration and lumen formation were (60.2 卤8.7)%, 31.3 卤4.5 and 17.2 卤3.3, respectively, which were significantly lower than those in the control group (P0.01). In SB203580 group, HUVECs proliferation rate [(79.6 卤8.9)%], migration number (21.6 卤4.3) and lumen formation number (23.5 卤4.3) were significantly lower than those in control group (P0.05). The proliferation rate of HUVECs, the number of migration and the number of lumen formation in TLR4-siRNA LPS,B203580 LPS group were significantly lower than those in LPS group (P0.01). Compared with the control group, the expression of VEGF,p-p38 protein increased significantly in LPS group, decreased in TLR4-siRNA group and SB203580 group, and decreased in TLR4-siRNA LPS group and SB203580 LPS group compared with LPS group. Conclusion TLR4 can promote angiogenesis in pancreatic carcinoma, and its mechanism is related to the activation of p38 MAPK signaling pathway and the promotion of VEGF expression.
【作者单位】：江苏省连云港市赣榆区人民医院消化内科;上海复旦大学附属华东医院消化内科;第二军医大学附属长海医院消化内科;
【基金】：连云港市卫生局科研项目(1427) 江苏省卫生厅科研项目(Y201420)
【分类号】：R735.9

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