IL-17及其受体调控DLL4-Notch信号通路影响甲状腺乳头状癌新生血管生成

IL-17/IL-17R regulate DLL4-Notch signaling pathway in the angiogenesis of papillary thyroid carcinoma

目的研究白介素-17(IL-17)/白介素-17受体(IL-17R)调控DLL4-Notch信号通路影响甲状腺乳头状癌血管生成的机制。方法建立甲状腺乳头状癌细胞(TPC-1)-内皮细胞共培养体系,检测50 ng/ml IL-17刺激剂对共培养系统中人脐静脉内皮细胞(HUVECs)增殖、迁移、成管能力的影响。Western blot法检测共培养体系中HUVECs DLL4-Notch信号通路和血管新生蛋白表达水平。结果50 ng/ml重组人IL-17A干预可显著促进共培养体系中HUVECs的增殖、迁移和成管能力(P<0.01)。pLKO.1-EGFP-Puro-IL-17R转染的TPC-1细胞共培养HUVECs经50 ng/ml重组人IL-17A干预6 h后,细胞中DLL4、Notch、HES、HEY和血管内皮细胞生长因子受体1(VEGFR1)、血管内皮细胞生长因子受体2(VEGFR2)的表达水平得到不同程度的上调,与对照组比较差异有统计学意义(P<0.01)。DLL4-Notch通路抑制剂DAPT干预可显著抑制IL-17刺激剂对共培养体系细胞中HES、HEY、VEGFR-1、VEGFR-2蛋白表达增加作用(P<0.01)。结论IL-17/IL-17R可能通过DLL4-Notch信号通路促进甲状腺乳头状癌血管生成。

Objective To explore the effects of interleukin(IL)-17/interleukin-17 receptor(IL-17R)on the angiogenesis of the endothelial cells co-cultured with cancer cells through DLL4-Notch signaling pathway and its molecular mechanism.Methods Cancer-endothelial cell co-culture model was established using the Transwell system.The effects of human recombinant IL-17A at 50 ng/ml on the migration of human umbilical vein endothelial cells(HUVECs)in the co-culture system were determined,the proliferation and angiogenesis of HUVECs was observed in co-culture system stimulated by human recombinant IL-17A,the angiogenesis ability of HUVECs was tested by tube formation assay,the proliferation of HUVECs was detected using CCK-8 assay.The expression of DLL4-Notch signaling pathway and angiogenesis protein in each group were detected by Western blot.Results 50 ng/ml human recombinant IL-17A could promote the migration of HUVECs in co-culture system.Treatment with 50 ng/ml human recombinant IL-17A significantly enhanced the proliferation and angiogenesis ability of the HUVECs in coculture system(P0.01).The expression of DLL4-Notch signaling pathway and angiogenesis-related proteins in co-culture system significantly increased compared with those in control group.Conclusion IL-17/IL-17R promotes DLL4-Notch signaling pathway in the angiogenesis of papillary thyroid carcinoma.