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rhTNF联合环磷酰胺对胶质瘤的靶向作用


秦丽娟1,王 健1,王海涛2,贾永森3,周洪霞4,王树华5   

  1. (1.河北联合大学基础医学院生理学教研室，河北 唐山 063000；2.河北联合大学基础医学院组织学与胚胎学教研室，河北 唐山 063000；3. 河北联合大学中医学院，河北 唐山 063000；4.河北联合大学基础医学院解剖学教研室，河北 唐山 063000； 5.河北联合大学基础医学院药理学教研室，河北 唐山063000)
  • 收稿日期:2013-01-17 出版日期:2013-07-28 发布日期:2013-08-17
  • 通讯作者: 秦丽娟(Tel: 0315-3725606,E-mail: qinlj2002@yahoo.com.cn) E-mail:qinlj2002@yahoo.com.cn
  • 作者简介:秦丽娟(1975-)，女，内蒙古自治区赤峰市人，副教授，医学博士，主要从 事脑肿瘤防治研究。
  • 基金资助:

    河北省卫生厅科学研究基金资助课题（20120144）

Targeting effect of rhTNF combined with cyclophosphamide on glioma

QIN Li-juan1,WANG Jian1,WANG Hai-tao2,JIA Yong-sen3,ZHOU Hong-xia4
,  WANG Shu-hua5   

  1. 1.   Department of Physiology,College of Basic Medical Sciences,Hebei United University,Tangshan 063000,China; 2. Department of  Histology and Embryology,College of Basic Medical Sciences,Hebei United University,Tangshan 063000,China; 3. College of Traditional Chinese Medicine，Hebei United University，Tangshan 063000,China; 4. Department of Anatomy,College of Basic Medical Sciences,Hebei United University,Tangshan 063000,China; 5. Department of Pharmacology,College of Basic Medical Sciences,Hebei United University,Tangsh
    an 063000,China)
  • Received:2013-01-17 Online:2013-07-28 Published:2013-08-17

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摘要：

目的：探讨重组人肿瘤坏死因子(rhTNF)联合环磷酰胺(CTX)对胶质瘤的靶向作用,并阐明其作用机制。方法：构建C6胶质瘤大鼠模型，将大鼠分为rhTNF组(n=10)、CTX组(n=10)及rhTNF -Dex-CTX组(n=10)。免疫荧光法观察肿瘤坏死因子受体1(TNFR1)在胶质瘤组织中的表达；利用125I-rhTNF，通过放射配基结合受体分析法检测大鼠脑组织和胶质瘤组织中rhTNF水平；ELISA法检测大鼠脑组织和胶质瘤组织中CTX水平；观察rhTNF、CTX及rhTNF-Dex-CTX偶联物对胶质瘤大鼠生存时间的影响。结果：TNFR1在胶质瘤细胞中的表达明显高于肿瘤血管内皮细胞。rhTNF在胶质瘤组织中与TNFR1的结合量明显高于正常脑组织(P<0.01)。 CTX组大鼠脑组织和胶质瘤组织中CTX水均较低；与CTX组和大鼠正常脑组织比较，rhTNF-Dex-CTX组大鼠胶质瘤组织内CTX的水平明显升高(P<0.01)。与CTX组和rhTNF组比较，rhTNF-Dex-CTX组大鼠的生存时间明显延长(P<0.01)。结论：rhTNF-Dex-CTX可能是通过TNFR1增强CTX对胶质瘤的靶向作用。

关键词: 胶质瘤, 重组人肿瘤坏死因子,  , 环磷酰胺,  , rhTNF-Dex-CTX偶联物

Abstract:

Objective To investigate the targeting effect of recombinant human tumor necrosis factor(rhTNF)combined with cyclophosphamide (CTX) on glioma and to clarify its mechanism.Methods C6 glioma rat models were established and divided into  rhTNF group(n=10),CTX group(n=10) and rhTNF-Dex-CTX group(n=10).The immunofluorescence method was used to observe tumor necrosis factor receptor 1(TNFR1) expression in glioma tissue; radioligand receptor binding analysis  was performed to determine the rhTNF concentration in brain tissue and glioma tissue; ELISA assay was used to detect the CTX levels in brain tissue and glioma tissue; the influence of rhTNF, CTX and rhTNF-Dex-CTX in  survival time of glioma rats was observed.Results The TNFR1 expression in glioma cells was significantly higher than that in tumor vascular endothelial cells.The amount of rhTNF combined with TNFR1 in glioma tissue was significantly higher than that in normal brain tissue (P<0.01).The CTX levels in the brain tissue and glioma tissue of the rats in CTX group were lower; compared with CTX group,the CTX level  in glioma tissue of the rats in rhTNF-Dex-CTX group was significantly increased;compared with CTX and rhTNF groups,the survival time of the  glioma rats in rhTNF-Dex-CTX group was significantly prolonged(P<0.01).Conclusion rhTNF-DexCTX may increase targeting effect of CTX on glioma by combining with TNFR1.

Key words: glioma, recombinant human tumor necrosis factor, cyclophosphamide, rhTNF-Dex-CTX conjugates

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