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Multidrug-resistant Phenotype of Disease-oriented Panels of Human Tumor Cell Lines Used for Anticancer Drug Screening

Laboratory of Drug Discovery Research and Development [L. W., A. M. S., S. F. S., L. M., M. R. B., R. H. S.], and Information Technology Branch [K. D. P.], Developmental Therapeutics Program, and Biometric Research Branch [A. D. K., L. V. R.], Cancer Therapy Evaluation Program, Division of Cancer Treatment, National Cancer Institute; and Program Resources Incorporated [A. M., D. A. S.], National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702

Disease-oriented panels of human tumor cell lines used by the National Cancer Institute for large-scale in vitro anticancer drug screening were evaluated for multidrug-resistant phenotype at the functional (in vitro drug sensitivity) and molecular levels. The cell line panels manifested a broad range of sensitivities to drugs typically associated with multidrug resistance (MDR) as well as to drugs not associated with MDR. Individual cell lines displayed unique and characteristic profiles of response. Patterns of correlated response were observed among, but not between, MDR and non-MDR drugs. Strong evidence of correlated response was limited to drugs sharing an intracellular mechanism of action. Several tumor cell lines exhibited a high degree of resistance to MDR drugs and relative sensitivity to non-MDR drugs, contained high levels of MDR-1 mRNA, and expressed cell surface P-glycoprotein detectable with one or more monoclonal antibodies. Parallel expression of all of these features representing the classic MDR phenotype was observed among members of the colon and renal tumor panels. Certain individual cell lines among other panels (lung, ovarian, melanoma, and central nervous system) also manifested some aspects of the MDR phenotype to various extents. Identification of MDR cell lines used for large-scale in vitro anticancer drug screening will facilitate interpretation of data in a way which may allow identification of new drug leads of potential value in treatment of MDR tumor cell populations.

¹ To whom requests for reprints should be addressed, at Laboratory of Drug Discovery Research and Development, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute-Frederick Cancer Research and Development Center, Building 1052, Room 121, Frederick, MD 21702-1201.

Received 10/25/91. Accepted 3/20/92.

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