腺病毒介导的TEM8抑制小鼠在体胶质瘤模型的血管生成作用  

Inhibitory effect of recombinant adenovirus expressing TEM8 gene against angiogenesis in mouse model of glioma

作　　者：陈宏颉[1,2] 王守森[1] 郑兆聪[1] 王如密[1] 

机构地区：[1]南京军区福州总医院神经外科,福州350025 [2]福建医科大学福总临床学院,福州350025

出　　处：《第二军医大学学报》2011年第8期860-863,共4页Academic Journal of Second Military Medical University

摘　　要：目的探讨基于TEM8的腺病毒(Ad-TEM8)对小鼠胶质瘤G422细胞系体内外模型的生长抑制及其抗血管的生成作用。方法连续皮下注射Ad-TEM8使其激活小鼠免疫系统并收集小鼠脾淋巴细胞,将该细胞与G422细胞体外共培养,检测G422细胞的生长抑制率,并应用ELISOT检测该免疫激活淋巴细胞在体外分泌IFN-γ的能力。另构建皮下荷G422昆明小鼠在体肿瘤模型,并连续皮下注射Ad-TEM8后检测肿瘤生长速度以及瘤内血管抑制效应。结果 Ad-TEM8能有效激发小鼠产生具有肿瘤生长抑制作用的毒性效应淋巴细胞,并分泌IFN-γ。Ad-TEM8皮下注射诱导的细胞毒性作用能有效抑制在体G422肿瘤生长,产生明显的血管生成抑制作用。结论 Ad-TEM8可诱导小鼠产生细胞毒性细胞、抑制在体和体外肿瘤细胞生长,其在体抑制肿瘤生长作用机制之一可能是抑制肿瘤内血管生成。TEM8可能成为抗胶质瘤血管生成治疗的新靶标。Objective To evaluate the inhibitory effects of recombinant adenovirus carrying TEM8（Ad-TEM8） against angiogenesis and growth of mouse glioma G422 cells in vitro and in vivo.Methods The Ad-TEM8 was constructed and subcutaneously injected to immunize Kunming mice,and then the splenic lymphocytes were collected for co-culture with G422 cells in vitro.The growth inhibition of G422 cells was observed and IFN-γ secretion by the activated lymphocytes were examined by ELISOT method.In addition,the anti-tumor and anti-angiogenesis effects of Ad-TEM8 were observed in Kunming mice carrying G422 xenografts.Results Ad-TEM8 effectively stimulated the generation of cytotoxic T lymphocytes（CTLs） in Kunming mice and the secretion of IFN-γ.Subcutaneous injection of Ad-TEM8-induced cytotoxicity effectively inhibited in vivo tumor growth and angiogenesis.Conclusion Ad-TEM8 can induce CTLs in mice,inhibit tumor growth in vitro and in vivo,and disrupt tumor vasculature.The anti-angiogenesis effect might be a mechanism for its in vivo anti-tumor effect;and TEM8 may serve as a novel target for anti-angiogenesis therapy of glioma.

关 键 词：神经胶质瘤 TEM8 腺病毒 G422细胞 病理性新生血管化 

分 类 号：R739.41[医药卫生—肿瘤]