Patterns of cross-resistance in a multidrug-resistant small-cell lung carcinoma cell line.
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.
Cole
S P
SP
Department of Oncology, Queen's University, Kingston, Ontario, Canada.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000963:Antimetabolites / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D018288:Carcinoma, Small Cell / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000502:physiology; D011720:Pyrazoles / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D000963:Antimetabolites; D008562:Membrane Glycoproteins; D011720:Pyrazoles