ROLE OF PROTEIN-KINASE-BETA ISOZYME IN MULTIDRUG-RESISTANCE IN MURINELEUKEMIA P388 ADR CELLS/

To define a role of protein kinase C (PKC) in multidrug resistance (MD R), we examined the influence of PKC isozyme specific antibodies deliv ered intracellularly, on drug sensitivity and drug accumulation in P38 8/ADR cells. Drug sensitive (P388) and drug resistant (P388/ADR) cells were permeabilized at 4 degrees C with L-lysolecithin and were incuba ted with rabbit anti-PKC, alpha, beta antibodies, or normal rabbit ser um for 10 minutes at 37 degrees C. Daunorubicin (DNR) accumulation and drug sensitivity were studied by flow cytometry and MTT assay, respec tively. Anti-PKC beta antibody partially corrected drug accumulation d efect and completely reversed resistance to DNR. Anti-PKC alpha antibo dy had no effect on either parameter of MDR. These results suggest tha t PKC beta plays an important role in MDR in P388/ADR cells. Furthermo re, the technique of intracellular delivery of antibodies provides a n ew approach to discern the role of PKC isoforms in multidrug resistanc e in various tumor cells.