Derivation and preliminary characterisation of adriamycin resistant lines of human lung cancer cells

Abstract

We have produced adriamycin (ADM)-resistant variants of the human lung cancer cell lines NCI-H69 (small cell), MOR (adenocarcinoma) and COR-L23 (large cell) but have failed to produce resistant variants of two other small cell lines. In each case, the derivation protocol took 7-9 months and included a period of drug-free growth. All three resistant lines show reduced cellular content of ADM after 1 h exposure when compared with their controls. During prolonged incubation of control and resistant NCI-H69 cells in 0.4 microgram ml-1 ADM, the ADM content of resistant cells was 6-7 times lower than that of control cells. The ratio of ADM doses to suppress growth of the two lines, however, was in the range of 40-200X. The ADM-resistant variant of NCI-H69 was also resistant to vincristine, colchicine, VP16, mitozantrone, 4' epiadriamycin and 4' deoxyadriamycin, somewhat resistant to melphalan but not resistant to aclacinomycin A, bleomycin of CCNU. The resistance to ADM could be partially overcome by the use of verapamil, an inhibitor of calcium transport.