Drug resistance in human lung cancer cell lines: cross-resistance studies and effects of the calcium transport blocker, verapamil.

We have developed multi-drug resistant variants of three human lung cancer cell lines by growth in increasing concentrations of adriamycin (ADM). Each of the lines shows reduced ADM content after acute drug exposure when compared with the corresponding parent line. The resistance to ADM may in each case be partially overcome by the concurrent use of 6.6 microM verapamil (VRP) (a calcium transport blocker). In small cell line NCI-H69 the growth inhibitory effect of VRP alone is greater in the resistant variant than in the parent line. Little or no change in the ADM sensitivity of parent cells is brought about by concentrations of VRP up to 15-20 microM. In the resistant line, a dose-related effect of VRP is seen with little effect below 1.0 microM and a gradual loss of resistance at higher doses. ADM-resistant cells of line NCI-H69 show only a small degree of resistance to two anthracyclines (aclacinomycin A and Ro 31-1215). This can be further reduced when these drugs are combined with verapamil.