Multidrug-resistant phenotype of disease-oriented panels of human tumor cell lines used for anticancer drug screening.
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.
Laboratory of Drug Discovery Research and Development, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702.
L
L
Wu
A M
AM
Smythe
S F
SF
Stinson
L A
LA
Mullendore
A
A
Monks
D A
DA
Scudiero
K D
KD
Paull
A D
AD
Koutsoukos
L V
LV
Rubinstein
M R
MR
Boyd
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D002460:Cell Line; D004273:DNA, Neoplasm / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics; D008969:Molecular Sequence Data; D009369:Neoplasms; D009838:Oligodeoxyribonucleotides; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger