Multiple drug-resistance in variant of a human non-small cell lung carcinoma cell line, DLKP-A.
A 300-fold adriamycin resistant variant (DLKP-A) of the human lung squamous cell carcinoma line DLKP was established by stepwise selection in increasing concentrations of adriamycin. Different levels of cross-resistance were observed towards VP-16, VM-26, colchicine, vincristine and, somewhat unexpectedly, cis-platin. Resistance was stable for at least 3 months in culture in the absence of drug. P-glycoprotein overexpression was detected by immunofluorescence and Western Blotting, and a direct causal role for P-glycoprotein overexpression in the resistant phenotype was established by transfection with an mdr1 specific antisense oligonucleotide. A modified cryopreservation procedure was necessary for the resistant variant line. The resistant population displays clonal heterogeneity with respect to resistance level. A higher frequency of double minute chromosomes was observed in DLKP-A when compared with the parental cell line.
National Cell and Tissue Culture Centre/Bioresearch Ireland, Dublin City University, Glasnevin.
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M
Clynes
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A
Redmond
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E
Moran
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U
Gilvarry
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002871:Chromosome Banding; D046508:Culture Techniques / Q000379:methods; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D014644:Genetic Variation; D006023:Glycoproteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008677:Metaphase; D008875:Middle Aged; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006023:Glycoproteins; D016376:Oligonucleotides, Antisense; D004317:Doxorubicin