Selective inhibition of hepatoma cells using diphtheria toxin A under the control of the promoter/enhancer region of the human alpha-fetoprotein gene.
Jpn J Cancer Res
; 91(3): 343-50, 2000 Mar.
Article
en En
| MEDLINE
| ID: mdl-10760695
ABSTRACT
We constructed a plasmid containing human alpha-fetoprotein (AFP) promoter/enhancer to direct the cell type-specific expression of diphtheria toxin fragment A (DTA), designated as pAF-DTA, to AFP-producing hepatocellular carcinoma cells. The transfection was carried out with cationic liposomes (DMRIE-C) and the expression of the DTA gene was confirmed by a northern blot analysis. When pAF-DTA was transfected, the growth of AFP-positive HuH-7 cells was inhibited, whereas growth inhibition was not observed in AFP-negative MKN45 cells. In this experiment, the secretion of AFP was similarly suppressed, but the secretion of carcinoembryonic antigen from MKN45 was not altered. pAF-DTA could also exert its growth inhibitory effect on PLC, a cell line with a low level of AFP. However, no inhibitory effect of pAF-DTA was observed on the proliferation of primary hepatocyte cells. Furthermore, transfection experiments in which HuH-7 and splenic stromal cells were co-cultured revealed the growth inhibition by pAF-DTA to be selective in HuH-7 cells. Finally, the growth of HuH-7 transplanted on BALB/c nu/nu mice was inhibited by the direct injection of pAF-DTA/liposome complex into a tumor mass. These results suggest that use of pAF-DTA may be potentially useful as a novel approach for the selective treatment of tumor cells producing AFP even at low levels, without affecting other types of cells.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Terapia Genética
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Alfa-Fetoproteínas
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Carcinoma Hepatocelular
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Toxina Diftérica
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Vectores Genéticos
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Neoplasias Hepáticas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Jpn J Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2000
Tipo del documento:
Article
País de afiliación:
Japón