Altered Protein Kinase C (PKC) Isoforms in Non-Small Cell Lung Cancer Cells: PKC Promotes Cellular Survival and Chemotherapeutic Resistance

Drugs that target protein kinase C (PKC) are now being evaluated in patients with non-small cell lung cancer (NSCLC), but the role of PKC in NSCLC cells remains unclear. We report here that NSCLC cell lines show enhanced phosphorylation and altered expression of specific PKC isoforms compared with normal lung epithelial cells. PKC inhibition variably increased apoptosis, with rottlerin, a PKC inhibitor, being most effective and potentiating chemotherapy-induced apoptosis, especially with trastuzumab. Consistent with PKC being anti-apoptotic in NSCLC cells, transient transfection of a kinase-dead mutant of PKC increased apoptosis and potentiated chemotherapy-induced apoptosis. Our studies provide a rationale for targeting PKC isoforms in NSCLC cells, especially PKC .