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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