GENE-TRANSFER OF HUMAN TNF-ALPHA INTO GLIOBLASTOMA CELLS PERMITS MODULATION OF MDR1 EXPRESSION AND POTENTIATION OF CHEMOSENSITIVITY

被引：32

作者：

WALTHER, W ^{[1
]}

STEIN, U ^{[1
]}

PFEIL, D ^{[1
]}

机构：

[1] MAX DELBRUCK CTR MOLEC MED,D-13122 BERLIN,GERMANY

来源：

INTERNATIONAL JOURNAL OF CANCER | 1995年 / 61卷 / 06期

关键词：

D O I：

10.1002/ijc.2910610615

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Despite substantial advances in the surgery, radiotherapy and chemotherapy of gliomas, the prognosis of patients with glioblastomas has still not improved. Disappointing results in chemotherapy of glioblastomas resulting from multi-drug resistance (MDR) prompted us to investigate the influence of cytokine gene transfer in glioblastoma cells on the expression of P-glycoprotein and on chemosensitivity of transduced cells. Several investigations have shown that malignant gliomas express P-glycoprotein at high levels. The P-glycoprotein is a product of the multi-drug resistance gene (mdr1) and functions as an energy-dependent efflux pump which decreases drug accumulation and cytotoxicity. Since tumour necrosis factor alpha (TNF alpha) is a powerful anti-cancer agent used in clinical trials and gene therapy protocols, this cytokine gene was chosen for the present investigations. Transduction of the human TNF alpha (hTNF) gene carrying retroviral vector pN2tk-hTNF into U373MG human glioblastoma cells resulted in expression and secretion of biologically active hTNF. Release of transduced hTNF reduces P-glycoprotein expression and is associated with enhanced rhodamine-123 uptake and potentiation of cytotoxicity of the MDR-relevant drugs vincristine and doxorubicin. Furthermore, the transfected cell clones showed a reduced growth rate compared to the parental cells. (C) 1995 Wiley-Liss, Inc.

引用

页码：832 / 839

页数：8

共 22 条

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