dihydropyridines and Thymoma

The requirement of P-glycoprotein, a product of the multidrug resistance (MDR)1 gene, for natural killer (NK) cell-mediated cytotoxicity was examined by using a human NK-like cell line, YTN, which is cytotoxic toward JY cells. YTN cells express P-glycoprotein, a judged by flow cytometry and polymerase chain reaction of reverse-transcribed mRNA. YTN cell-mediated cytotoxicity was inhibited by MDR-reversing reagents as well as the F(ab')2 fragment of a monoclonal antibody against P-glycoprotein. Furthermore, antisense oligonucleotides for MDR1 mRNA inhibited expression of P-glycoprotein as well as YTN cell-mediated cytotoxicity. Thus, this study provides firm evidence that P-glycoprotein plays an essential role in cell-mediated cytotoxicity.

Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Cell Line; Cell Survival; Cytotoxicity, Immunologic; Dihydropyridines; Drug Resistance, Multiple; Humans; Killer Cells, Natural; Nicardipine; Oligonucleotides, Antisense; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyrazoles; RNA, Messenger; Thymoma; Thymus Neoplasms; Transcription, Genetic; Tumor Cells, Cultured