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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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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
1995
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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. |
format | Online Article Text |
id | pubmed-5920759 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1995 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
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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