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Selective Inhibition of Hepatoma Cells Using Diphtheria Toxin A under the Control of the Promoter/Enhancer Region of the Human α‐Fetoprotein Gene

We constructed a plasmid containing human α‐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)...

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Detalles Bibliográficos
Autores principales: Kunitomi, Michito, Takayama, Eiji, Suzuki, Satoshi, Yasuda, Tatsuji, Tsutsui, Ken, Nagaike, Kazuhiro, Hiroi, Sadayuki, Tadakuma, Takushi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926372/
https://www.ncbi.nlm.nih.gov/pubmed/10760695
http://dx.doi.org/10.1111/j.1349-7006.2000.tb00951.x
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author Kunitomi, Michito
Takayama, Eiji
Suzuki, Satoshi
Yasuda, Tatsuji
Tsutsui, Ken
Nagaike, Kazuhiro
Hiroi, Sadayuki
Tadakuma, Takushi
author_facet Kunitomi, Michito
Takayama, Eiji
Suzuki, Satoshi
Yasuda, Tatsuji
Tsutsui, Ken
Nagaike, Kazuhiro
Hiroi, Sadayuki
Tadakuma, Takushi
author_sort Kunitomi, Michito
collection PubMed
description We constructed a plasmid containing human α‐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.
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spelling pubmed-59263722018-05-11 Selective Inhibition of Hepatoma Cells Using Diphtheria Toxin A under the Control of the Promoter/Enhancer Region of the Human α‐Fetoprotein Gene Kunitomi, Michito Takayama, Eiji Suzuki, Satoshi Yasuda, Tatsuji Tsutsui, Ken Nagaike, Kazuhiro Hiroi, Sadayuki Tadakuma, Takushi Jpn J Cancer Res Article We constructed a plasmid containing human α‐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. Blackwell Publishing Ltd 2000-03 /pmc/articles/PMC5926372/ /pubmed/10760695 http://dx.doi.org/10.1111/j.1349-7006.2000.tb00951.x Text en
spellingShingle Article
Kunitomi, Michito
Takayama, Eiji
Suzuki, Satoshi
Yasuda, Tatsuji
Tsutsui, Ken
Nagaike, Kazuhiro
Hiroi, Sadayuki
Tadakuma, Takushi
Selective Inhibition of Hepatoma Cells Using Diphtheria Toxin A under the Control of the Promoter/Enhancer Region of the Human α‐Fetoprotein Gene
title Selective Inhibition of Hepatoma Cells Using Diphtheria Toxin A under the Control of the Promoter/Enhancer Region of the Human α‐Fetoprotein Gene
title_full Selective Inhibition of Hepatoma Cells Using Diphtheria Toxin A under the Control of the Promoter/Enhancer Region of the Human α‐Fetoprotein Gene
title_fullStr Selective Inhibition of Hepatoma Cells Using Diphtheria Toxin A under the Control of the Promoter/Enhancer Region of the Human α‐Fetoprotein Gene
title_full_unstemmed Selective Inhibition of Hepatoma Cells Using Diphtheria Toxin A under the Control of the Promoter/Enhancer Region of the Human α‐Fetoprotein Gene
title_short Selective Inhibition of Hepatoma Cells Using Diphtheria Toxin A under the Control of the Promoter/Enhancer Region of the Human α‐Fetoprotein Gene
title_sort selective inhibition of hepatoma cells using diphtheria toxin a under the control of the promoter/enhancer region of the human α‐fetoprotein gene
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5926372/
https://www.ncbi.nlm.nih.gov/pubmed/10760695
http://dx.doi.org/10.1111/j.1349-7006.2000.tb00951.x
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