Targeting protein kinase C beta enhances cell death of non-small cell lung cancer cells.

摘要: Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006 A127 The protein kinase C (PKC) family consists of structurally related serine-threonine kinases that influence drug resistance and cell survival various cancers. In this study we identified two the classical PKC isoforms, PKC-α PKC-β played an important role non-small lung cancer (NSCLC) cells. Various NSCLC cells (H1734, A549, H226, H1703, H292) expressed high levels phosphorylated PKC-α, PKC-μ when compared to normal human tracheobronchial epithelial (NHTBE) The PKC-δ or PKC-ζ, ι/λ were reduced NHTBE. Knock down expression by small interfering (si) RNAs, siPKCβ alone combined siPKCα/β a lesser extent siPKCα inhibited cAMP response element (CRE)-binding (CREB) transcription factor H1734 line. Immunofluorescence analysis revealed knock-downs also induced changes phosphorylation PKCβ CREB as well translocation nuclear cytoplasm. Phosphorylation upstream including ERK1/2 RSK was observed Western blotting following knock kinases. genes Bcl-2 Bcl-xl siPKCα/β, which accompanied induction DNA fragmentation apoptosis measured TUNEL. Treatment with inhibits proliferation up 50%, did not occur using siPKCα. Finally, combining other drugs increased sensitivity cytotoxcicty. These data illustrate usefulness siRNA directed against suppress growth tumor selectively overexpress sensitize them may be useful prevention setting for risk populations reduce level cytotoxic drugs.