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Acute Induction of Adriamycin‐resistance in Human Colon Carcinoma HT‐29 Cells Exposed to a Sublethal Dose of Adriamycin
Author(s) -
Tomida Akihiro,
Naito Mikihiko,
Tsuruo Takashi
Publication year - 1995
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1995.tb03043.x
Subject(s) - drug resistance , p glycoprotein , pharmacology , cell culture , verapamil , population , doxorubicin , cancer cell , medicine , chemotherapy , biology , cancer , multiple drug resistance , genetics , environmental health , microbiology and biotechnology , calcium
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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