A diphtheria toxin-epidermal growth factor fusion protein is cytotoxic to human glioblastoma multiforme cells.

Liu, Tie Fu; Cohen, Kimberley A; Ramage, Jason G; Willingham, Mark C; Thorburn, Andrew M; Frankel, Arthur E

Liu, Tie Fu; Cohen, Kimberley A; Ramage, Jason G; Willingham, Mark C; Thorburn, Andrew M; Frankel, Arthur E.

Afiliación

Liu TF; Department of Cancer Biology and Pathology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.

Cancer Res ; 63(8): 1834-7, 2003 Apr 15.

Article en En | MEDLINE | ID: mdl-12702570

RESUMEN

The cytotoxicity of a diphtheria toxin-human epidermal growth factor fusion protein (DAB(389)EGF) was tested against 14 human glioma cell lines. After cells were cultured for 48 h with various concentrations of DAB(389)EGF, the percentage reduction in thymidine incorporation was determined. For 13 of 14 cell lines, potent cytotoxicity was observed, with IC(50)s of 0.4-50 pM. The epidermal growth factor receptor (EGFR) density of these cell lines was determined by immunofluorescence microscopy, flow cytometry, and radioligand binding. These assays correlated well with each other and demonstrated EGFR levels of 15,000-230,000/cell for 13 of 14 cell lines. The cell line U138MG, which lacked EGFR, was the only cell line insensitive to DAB(389)EGF. Linear regression analysis showed a good correlation between EGFR density and DAB(389)EGF sensitivity (P < 0.001) and between results of flow cytometry and radiolabeled binding assays of EGFR density (P = 0.01). DAB(389)EGF may have potential for intracranial therapy of EGFR-positive glioblastomas.

Asunto(s)

Neoplasias Encefálicas/tratamiento farmacológico; Toxina Diftérica/farmacología; Factor de Crecimiento Epidérmico/farmacología; Glioblastoma/tratamiento farmacológico; Proteínas Recombinantes de Fusión/farmacología; Neoplasias Encefálicas/metabolismo; Carcinoma de Células Escamosas/tratamiento farmacológico; Carcinoma de Células Escamosas/metabolismo; Toxina Diftérica/genética; Toxina Diftérica/metabolismo; Ensayos de Selección de Medicamentos Antitumorales; Factor de Crecimiento Epidérmico/genética; Factor de Crecimiento Epidérmico/metabolismo; Receptores ErbB/metabolismo; Citometría de Flujo; Glioblastoma/metabolismo; Humanos; Concentración 50 Inhibidora; Cinética; Microscopía Fluorescente; Proteínas Recombinantes de Fusión/genética; Células Tumorales Cultivadas

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Recombinantes de Fusión / Neoplasias Encefálicas / Glioblastoma / Toxina Diftérica / Factor de Crecimiento Epidérmico Límite: Humans Idioma: En Revista: Cancer Res Año: 2003 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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