壮观霉素B1诱导VEGFR2去SUMO化修饰抑制鼻咽癌血管生成  

Spectomycin B1 induces VEGFR2 de-SUMO modification to inhibit angiogenesis in nasopharyngeal carcinoma

作　　者：任庆[1] 张春艳 马晓芳[3] 成睿珍 边希云 肖晓琳 刘晓智[3] 周慧芳[4] REN Qing;ZHANG Chunyan;MA Xiuofang;CHENG Ruizhen;BIAN Xiyun;XIAO Xiaolin;LIU Xiaozhi;ZHOU Huifang(Department of Otorhinolaryngology,the Fifth Central Hospital of Tianjin,Tianjin,300450,China;Department of Pharmacy,Tianjin Binhai New Area Hospital of Traditional Chinese Medicine;Central Laboratory,the Fifth Central Hospital of Tianjin;Department of Otorhinolaryngology,Tianjin Medical University General Hospital)

机构地区：[1]天津市第五中心医院耳鼻咽喉科,天津300450 [2]天津市滨海新区中医医院药学科 [3]天津市第五中心医院中心实验室 [4]天津医科大学总医院耳鼻咽喉科

出　　处：《临床耳鼻咽喉头颈外科杂志》2019年第12期1181-1184,共4页Journal of Clinical Otorhinolaryngology Head And Neck Surgery

基　　金：国家自然科学基金项目(No:81471175,No:31671246)

摘　　要：目的:探讨壮观霉素B1抑制鼻咽癌血管生成的新机制,为鼻咽癌的靶向基因治疗提供理论依据。方法:以人鼻咽癌CNE1细胞为研究对象,分为对照组和壮观霉素B1组。Western blot法检测小泛素相关修饰蛋白(SUMO)1和血管内皮生长因子受体2(VEGFR2)蛋白表达水平,血管模拟形成实验检测CNE1细胞血管形成能力,流式细胞术检测细胞凋亡情况;建立鼻咽癌荷瘤鼠模型,给予壮观霉素B1治疗,测量肿瘤体积与重量,免疫组织化学方法检测CD31的蛋白表达并比较微血管密度。结果:壮观霉素B1能够使VEGFR2蛋白SUMO化修饰水平降低4.05倍,明显降低CNE1细胞血管形成能力,细胞凋亡率增加20.68%;在荷瘤鼠模型中,壮观霉素B1治疗能够抑制皮下肿瘤生长速度和重量,血管密度下降40.04%。结论:壮观霉素B1通过降低VEGFR2蛋白SUMO化修饰途径抑制鼻咽癌新生血管生成。Objective:To explore the new mechanism of spectomycin B1 in inhibiting angiogenesis of nasopharyngeal carcinoma and to provide a theoretical basis for targeted gene therapy of nasopharyngeal carcinoma.Method:Human nasopharyngeal carcinoma CNE1 cells were divided into two groups,the control group and spectomycin B1 group.Western blot was used to detect the expression levels of small ubiquitin-related modified protein(SUMO)1 and vascular endothelial growth factor receptor 2(VEGFR2).The angiogenesis assay was used to detect the angiogenic ability of CNE1 cells,and the apoptosis was detected by flow cytometry.The model of nasopharyngeal carcinoma-bearing mice was established,spectomycin B1 was administered,tumor volume and weight were measured,and protein expression of CD31 was detected by immunohistochemistry and microvessel density was compared.Result:Spectomycin B1 could reduce deSUMOylation of VEGFR2 protein by 4.05 times,significantly reduce the angiogenic ability of CNE1 cells,and increase the apoptosis rate by 20.68%.In the tumor-bearing mouse model,spectomycin B1 treatment could inhibit subcutaneous tumor growth rate and weight,and the blood vessel density decreased by 40.04%.Conclusion:Spectomycin B1 can inhibit neovascularization of nasopharyngeal carcinoma by inducing deSUMOylation of VEGFR2 protein.

关 键 词：鼻咽肿瘤 小泛素相关修饰蛋白 血管内皮生长因子受体2 壮观霉素B1 

分 类 号：R739.63[医药卫生—肿瘤]