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Patterns of cross-resistance in a multidrug-resistant small-cell lung carcinoma cell line

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Summary

H69AR is a multidrug-resistant human small-cell lung carcinoma cell line that was selected in doxorubicin and has previously been shown to be cross-resistant to a variety of natural-product-type anticancer drugs. H69AR is unlike many other multidrug-resistant cell lines in that it does not overexpress P-glycoprotein. In the present study, the drug sensitivity and cross-resistance patterns of H69AR cells were further characterized. A total of 15 drugs belonging to a number of chemical classes were screened. These compounds included anthracyclines, DNA binders (anthrapyrazoles, benzothiopyranoindazoles, and pyrazoloacridines), and lipophilic antifolates. The alkylating agent melphalan and the antimetabolite cytosine arabinofuranoside (Ara-C) were also tested. In general, the drug sensitivity and cross-resistance profiles of H69AR cells were consistent with those reported by others using other drug-resistant cell lines. However, there were several unexpected instances of cross-resistance. Thus, the H69AR cell line was more resistant than its parent cell line to the potent 3’-deamino-3’-(3-cyano-4-morpholinyl) doxorubicin, bisantrene, the pyrazoloacridine PD 114541, Ara-C, and melphalan. In addition, no cross-resistance to the four lipophilic antifolates tested, including trimetrexate, was found. The absence of a consistent pattern among the various drug-resistant cell lines indicates that assumptions about the efficacy of anticancer drugs in multidrug resistance should be made with caution.

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  1. Departments of Oncology and Pharmacology and Toxicology, Queen’s University, K7L 3N6, Kingston, Ontario, Canada

    S. P. C. Cole

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Supported by a grant from the National Cancer Institute of Canada Correspondence and proofs: S. P. C. Cole, Ph. D., Cancer Research Laboratories, Botterell Hall Rm 331. Queen’s University, Kingston, Ontario K7L 3N6 Canada, TEL 613-545-6358. FAX 613-544-9708

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Cole, S.P.C. Patterns of cross-resistance in a multidrug-resistant small-cell lung carcinoma cell line. Cancer Chemother Pharmacol 26, 250–256 (1990). https://doi.org/10.1007/BF02897225

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  • DOI: https://doi.org/10.1007/BF02897225

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