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Acute Induction of Adriamycin‐resistance in Human Colon Carcinoma HT‐29 Cells Exposed to a Sublethal Dose of Adriamycin

To study the mechanisms of the acute induction of drug resistance in cancer cells, we have established a model system in which adriamycin (ADM) induces immediate drug resistance. In this system, human colon carcinoma HT‐29 cells were pretreated for 1 h with a subtoxic dose of ADM (0.3 μg/ml) and inc...

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Detalles Bibliográficos
Autores principales: Tomida, Akihiro, Naito, Mikihiko, Tsuruo, Takashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 1995
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920759/
https://www.ncbi.nlm.nih.gov/pubmed/7730148
http://dx.doi.org/10.1111/j.1349-7006.1995.tb03043.x
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author Tomida, Akihiro
Naito, Mikihiko
Tsuruo, Takashi
author_facet Tomida, Akihiro
Naito, Mikihiko
Tsuruo, Takashi
author_sort Tomida, Akihiro
collection PubMed
description To study the mechanisms of the acute induction of drug resistance in cancer cells, we have established a model system in which adriamycin (ADM) induces immediate drug resistance. In this system, human colon carcinoma HT‐29 cells were pretreated for 1 h with a subtoxic dose of ADM (0.3 μg/ml) and incubated for 24 h in drug‐free medium. Then the cells were treated for 1 h with ADM, and the cell survival was determined in terms of colony‐forming ability. The survival of the pretreated cells was increased up to 100‐fold, as compared with that of untreated cells. Such increased survival, however, was observed only after high doses of ADM (2 to 8 μg/ml); more than 99% of the cells were killed. These results indicate that only a small fraction of ADM‐pretreated cells acquire the ADM‐resistant phenotype. Similar induced resistance was observed in five of seven subclones isolated from HT‐29 cells by limiting dilution, suggesting that the majority of cells in the parental HT‐29 population could acquire the ADM‐resistant phenotype. In the subclone HT‐29T9, the ADM pretreatment induced concomitant resistance to daunomycin, VP‐16, and VM‐26 but not to agents other than topoisomerase II inhibitors. The ADM‐induced drug resistance did not accompany MDR1 gene expression and could not be overcome by verapamil, a P‐glycoprotein inhibitor. The present system could be useful to study the acute induction mechanism(s) of ADM‐resistance, which could be relevant to clinical resistance in patients.
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spelling pubmed-59207592018-05-11 Acute Induction of Adriamycin‐resistance in Human Colon Carcinoma HT‐29 Cells Exposed to a Sublethal Dose of Adriamycin Tomida, Akihiro Naito, Mikihiko Tsuruo, Takashi Jpn J Cancer Res Article To study the mechanisms of the acute induction of drug resistance in cancer cells, we have established a model system in which adriamycin (ADM) induces immediate drug resistance. In this system, human colon carcinoma HT‐29 cells were pretreated for 1 h with a subtoxic dose of ADM (0.3 μg/ml) and incubated for 24 h in drug‐free medium. Then the cells were treated for 1 h with ADM, and the cell survival was determined in terms of colony‐forming ability. The survival of the pretreated cells was increased up to 100‐fold, as compared with that of untreated cells. Such increased survival, however, was observed only after high doses of ADM (2 to 8 μg/ml); more than 99% of the cells were killed. These results indicate that only a small fraction of ADM‐pretreated cells acquire the ADM‐resistant phenotype. Similar induced resistance was observed in five of seven subclones isolated from HT‐29 cells by limiting dilution, suggesting that the majority of cells in the parental HT‐29 population could acquire the ADM‐resistant phenotype. In the subclone HT‐29T9, the ADM pretreatment induced concomitant resistance to daunomycin, VP‐16, and VM‐26 but not to agents other than topoisomerase II inhibitors. The ADM‐induced drug resistance did not accompany MDR1 gene expression and could not be overcome by verapamil, a P‐glycoprotein inhibitor. The present system could be useful to study the acute induction mechanism(s) of ADM‐resistance, which could be relevant to clinical resistance in patients. Blackwell Publishing Ltd 1995-02 /pmc/articles/PMC5920759/ /pubmed/7730148 http://dx.doi.org/10.1111/j.1349-7006.1995.tb03043.x Text en
spellingShingle Article
Tomida, Akihiro
Naito, Mikihiko
Tsuruo, Takashi
Acute Induction of Adriamycin‐resistance in Human Colon Carcinoma HT‐29 Cells Exposed to a Sublethal Dose of Adriamycin
title Acute Induction of Adriamycin‐resistance in Human Colon Carcinoma HT‐29 Cells Exposed to a Sublethal Dose of Adriamycin
title_full Acute Induction of Adriamycin‐resistance in Human Colon Carcinoma HT‐29 Cells Exposed to a Sublethal Dose of Adriamycin
title_fullStr Acute Induction of Adriamycin‐resistance in Human Colon Carcinoma HT‐29 Cells Exposed to a Sublethal Dose of Adriamycin
title_full_unstemmed Acute Induction of Adriamycin‐resistance in Human Colon Carcinoma HT‐29 Cells Exposed to a Sublethal Dose of Adriamycin
title_short Acute Induction of Adriamycin‐resistance in Human Colon Carcinoma HT‐29 Cells Exposed to a Sublethal Dose of Adriamycin
title_sort acute induction of adriamycin‐resistance in human colon carcinoma ht‐29 cells exposed to a sublethal dose of adriamycin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920759/
https://www.ncbi.nlm.nih.gov/pubmed/7730148
http://dx.doi.org/10.1111/j.1349-7006.1995.tb03043.x
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