慢性应激介导Plexin A1-JAK2-STAT3通路刺激VEGF分泌促进胃癌血管生成  

Chronic stress-mediated Plexin A1-JAK2-STAT3 pathway stimulates VEGF secretion and promotes gastric cancer angiogenesis

作　　者：刘莹[1] 程蝶 彭禹桥 庞佳昱 鲁艳杰 李杨 李玉红[1] LIU Ying;CHENG Die;PENG Yu-qiao;PANG Jia-yu;LU Yan-jie;LI Yang;LI Yu-hong(Cancer Research Laboratory,Chengde Medical College,Chengde,Hebei 067000,China;Institute of Radiation Medicine,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China)

机构地区：[1]承德医学院肿瘤研究室,河北承德067000 [2]军事科学院军事医学研究院辐射医学研究所,北京100850

出　　处：《军事医学》2022年第10期737-743,共7页Military Medical Sciences

基　　金：河北省自然科学基金项目(H202040600);河北省科技厅“技术创新引导专项-科技工作会商”项目;河北省高校重点学科建设项目(病理学与病理生理学)[冀教高(2013)4号];承德医学院校级科研项目(202007,KY2021037)。

摘　　要：目的 探究异丙肾上腺素(ISO)模拟的慢性应激通过神经丛素A1-蛋白酪氨酸激酶2-信号转导与转录激活因子3(Plexin A1-JAK2-STAT3)通路对胃癌血管生成的影响。方法 利用慢病毒或通路抑制剂分别干扰MGC-803胃癌细胞中Plexin A1的表达或JAK2-STAT3信号通路,再联合利用20μmol/L浓度的ISO作用MGC-803细胞12 h后,收集细胞培养液,采用放射免疫法检测MGC-803细胞分泌血管内皮生长因子(VEGF)水平;用MGC-803细胞培养液进一步培养血管内皮细胞EA.hy926,分别利用CCK-8法、Transwell法、血管形成实验检测EA.hy926细胞的增殖、迁移和成管能力;Western印迹检测EA.hy926细胞中Plexin A1、VEGF受体2(VEGFR2)蛋白表达。结果 慢病毒干扰MGC-803细胞Plexin A1后,细胞VEGF分泌水平明显降低;干扰了Plexin A1表达的MGC-803细胞培养液培养EA.hy926细胞后,EA.hy926细胞中VEGFR2和Plexin A1表达明显减少,同时EA.hy926细胞增殖、迁移和成管能力显著降低;抑制MGC-803细胞中JAK2-STAT3信号通路,细胞VEGF分泌水平明显降低;利用MGC-803细胞培养液培养的血管内皮细胞EA.hy926的增殖、迁移和成管能力显著降低。结论 慢性应激通过胃癌细胞Plexin A1-JAK2-STAT3信号通路刺激VEGF分泌,促进胃癌血管生成。Objective To explore the effects of isoproterenol(ISO)-simulated chronic stress on gastric cancer angiogenesis through the Plexin A1-JAK2-STAT3 pathway. Methods The lentivirus or pathway inhibitor was used to intervene in the expression of Plexin A1 or JAK2-STAT3 signal pathway in MGC-803 gastric cancer cells respectively before ISO at the concentration of 20 μmol/L was also used to treat gastric cancer cells for 12 hours. The gastric cancer cell culture medium was collected,and the level of vascular endothelial growth factor(VEGF)secreted by gastric cancer cells was detected by radioimmunoassay. The gastric cancer cell culture medium was collected a second time to continue to culture vascular endothelial cells before the proliferation,migration and tube forming ability of vascular endothelial cells EA.hy926 were detected using the CCK-8 method,Transwell method and angiogenesis experiment respectively. Western blotting was used to detect the protein expressions of Plexin A1 and VEGFR2 in vascular endothelial cells. Results After lentivirus interfered with Plexin A1,the secretion level of VEGF in gastric cancer cells was significantly reduced. After vascular endothelial cells were cultured with gastric cancer cell culture medium that interfered with the expression of Plexin A1,the expressions of VEGFR2 and Plexin A1 in vascular endothelial cells were significantly reduced,so were the proliferation,migration,and tube-forming abilities of these cells. Inhibition of JAK2-STAT3 in gastric cancer cells signaling pathway resulted in significant reduction of the secretion level of VEGF in gastric cancer cells and of the proliferation,migration and tube-forming abilities of vascular endothelial cells cultured with gastric cancer cell culture medium. Conclusion Chronic stress promotes the angiogenesis of gastric cancer by stimulating the secretion of VEGF through the Plexin A1-JAK2-STAT3 signaling pathway in gastric cancer cells.

关 键 词：胃癌 血管生成 慢性应激 神经丛素A1 JAK2-STAT3 

分 类 号：R735.2[医药卫生—肿瘤]