Role of protein kinase beta isozyme in multidrug resistance in murine leukemia P388/ADR cells.
To define a role of protein kinase C (PKC) in multidrug resistance (MDR), we examined the influence of PKC isozyme specific antibodies delivered intracellularly, on drug sensitivity and drug accumulation in P388/ADR cells. Drug sensitive (P388) and drug resistant (P388/ADR) cells were permeabilized at 4 degrees C with L-lysolecithin and were incubated with rabbit anti-PKC, alpha, beta antibodies, or normal rabbit serum for 10 minutes at 37 degrees C. Daunorubicin (DNR) accumulation and drug sensitivity were studied by flow cytometry and MTT assay, respectively. Anti-PKC beta antibody partially corrected drug accumulation defect and completely reversed resistance to DNR. Anti-PKC alpha antibody had no effect on either parameter of MDR. These results suggest that PKC beta plays an important role in MDR in P388/ADR cells. Furthermore, the technique of intracellular delivery of antibodies provides a new approach to discern the role of PKC isoforms in multidrug resistance in various tumor cells.
Gollapudi
S
S
Division of Basic and Clinical Immunology, University of California, Irvine 92717, USA.
Soni
V
V
Thadepalli
H
H
Gupta
S
S
D000818:Animals; D003630:Daunorubicin / Q000493:pharmacokinetics / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D007527:Isoenzymes / Q000502:physiology; D007941:Leukemia P388 / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D011493:Protein Kinase C / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D004317:Doxorubicin; D011493:Protein Kinase C; D003630:Daunorubicin