转化生长因子α-PE40的细胞毒性及其与表皮生长因子受体表达的相关性

Cytotoxicity of TGF alpha-PE40 and correlation to expression of epidermal growth factor receptor.

作者信息

Berger D P, Herbstritt L, Hellerich U, Schulzke S, Dengler W A, Gallo M, Pastan I, Mertelsmann R, Fiebig H H

机构信息

Department of Internal Medicine I, Haematology/Oncology, University of Freiburg, Germany.

出版信息

Eur J Cancer. 1995 Nov;31A(12):2067-72. doi: 10.1016/0959-8049(95)00422-x.

DOI:10.1016/0959-8049(95)00422-x

PMID:8562167

Abstract

TGF alpha-PE40 is a chimeric protein composed of transforming growth factor alpha (TGF alpha) linked to a modified Pseudomonas exotoxin (PE40). We tested the in vitro cytotoxicity of TGF alpha-PE40 on 23 different solid human tumour xenografts established in nude mice and human bone marrow cells from healthy donors, utilising a modified clonogenic assay. In order to distinguish non-specific toxicity from the targeted effects of TGF alpha-PE40, epidermal growth factor receptor (EGFR) expression of the tumours studied was assessed by Northern blot, slot blot and immunohistochemistry. TGF alpha-PE40 demonstrated differential cytotoxicity on human tumour xenografts in the clonogenic assay. No toxicity on human bone marrow cells was observed. In vitro activity of TGF alpha-PE40 showed a significant correlation with the expression of EGF receptors as determined by immunohistochemistry and slot blot. Further studies will be performed in order to determine the in vivo activity of this compound in tumour-bearing nude mice.

摘要

转化生长因子α-绿脓杆菌外毒素40（TGFα-PE40）是一种嵌合蛋白，由与修饰的绿脓杆菌外毒素（PE40）相连的转化生长因子α（TGFα）组成。我们利用改良的克隆形成试验，测试了TGFα-PE40对在裸鼠中建立的23种不同的人实体肿瘤异种移植瘤以及来自健康供体的人骨髓细胞的体外细胞毒性。为了区分非特异性毒性与TGFα-PE40的靶向作用，通过Northern印迹、狭缝印迹和免疫组织化学评估了所研究肿瘤的表皮生长因子受体（EGFR）表达。在克隆形成试验中，TGFα-PE40对人肿瘤异种移植瘤表现出不同的细胞毒性。未观察到对人骨髓细胞的毒性。TGFα-PE40的体外活性与通过免疫组织化学和狭缝印迹测定的表皮生长因子受体表达显著相关。将进行进一步研究以确定该化合物在荷瘤裸鼠中的体内活性。