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[摘要]：Protein kinase C (PKC)epsilon, a member of the novel PKC family, has key roles in mitogenesis and survival in normal and cancer cells. PKC epsilon is frequently overexpressed in epithelial cancers, particularly in lung cancer. Using a short-hairpin RNA approach, here we established that PKCe is required for non-small cell lung carcinoma (NSCLC) growth in vitro as well as tumor growth when inoculated into athymic mice. Moreover, sustained delivery of a PKC epsilon-selective inhibitor peptide, epsilon V1-2, reduced xenograft growth in mice. Both RNA interference depletion and pharmacological inhibition of PKCe caused a marked elevation in the number of apoptotic cells in NSCLC tumors. PKC epsilon-depleted NSCLC cells show elevated expression of pro-apoptotic proteins of the Bcl2 family, caspase recruitment domain-containing proteins and tumor necrosis factor ligands/receptor superfamily members. Moreover, a Gene Set Enrichment Analysis revealed that a vast majority of the genes changed in PKC epsilon-depleted cells were also deregulated in human NSCLC. Our results strongly suggest that PKC epsilon is required for NSCLC cell survival and maintenance of NSCLC tumor growth. Therefore, PKC epsilon may represent an attractive therapeutic target for NSCLC. Oncogene (2012) 31, 2593-2600; doi:10.1038/onc.2011.428; published online 26 September 2011 |
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