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.