多药耐药（mdr）被称为对抗癌药物的交叉耐药性，与细胞外质膜上能量依赖性外输泵P-糖蛋白的表达有关，该蛋白是mdr1基因的产物。当人乳腺癌细胞MCF-7转染人类mdr1基因（BC-19细胞）时，它们的P-糖蛋白水平与对多柔比星产生抗性的细胞（MCF-7/ADR）相当，但对多柔比星和长春碱的抗性降低了10到50倍。我们现在证明，当BC-19细胞稳定转染了蛋白激酶Cα（PKCα）时，多柔比星和长春碱的抗性增加了；转染PKCα的野生型MCF-7细胞没有表现出任何药物抗性变化。PKCα转染的BC-19细胞抗药性增强与PKC活性提高和P-糖蛋白的磷酸化增加以及药物积累降低有关。PKC活化剂丙酸酯二丁酸进一步增强了对多柔比星的耐药性，并刺激了P-糖蛋白的磷酸化。这些结果表明，转染P-糖蛋白的细胞并加入PKC会导致mdr增加，而PKC可能是这一过程的重要调节因子。

Cross-resistance to anticancer drugs, termed multidrug resistance (mdr), has been functionally associated with the expression of a plasma membrane energy-dependent efflux pump, termed P-glycoprotein, the product of the mdr1 gene. When MCF-7 breast carcinoma cells were transfected with the human mdr1 gene (BC-19 cells), they expressed levels of P-glycoprotein equivalent to those of cells selected for resistance to doxorubicin (MCF-7/ADR) but exhibited 10- to 50-fold less resistance to doxorubicin and vinblastine. We have now demonstrated that when BC-19 cells were stably transfected with protein kinase C alpha (PKC alpha), resistance to doxorubicin and vinblastine was increased; wild-type MCF-7 cells transfected with PKC alpha did not exhibit any change in drug resistance. Increased resistance in PKC alpha-transfected BC-19 cells was associated with enhanced PKC activity and phosphorylation of P-glycoprotein and decreased drug accumulation. The PKC activator, phorbol dibutyrate, further increased resistance to doxorubicin and stimulated P-glycoprotein phosphorylation. These results demonstrate that transfection of P-glycoprotein-expressing cells with PKC resulted in increased mdr and that PKC may have served as an important modulator of this process.