Inhibition of protein kinase C-alpha expression in human A549 cells by antisense oligonucleotides inhibits induction of intercellular adhesion molecule 1 (ICAM-1) mRNA by phorbol esters.

摘要: We have identified 20-mer phosphorothioate oligodeoxynucleotides which potently (IC50 values of 100-200 nM) and specifically inhibit protein kinase C (PKC)-alpha mRNA expression in human lung carcinoma (A549) cells. These oligonucleotides target multiple, diverse sites on PKC-alpha including the AUG translation codon 3'-untranslated sequences. 2'-O-Methyl analogs these were without effect levels, suggesting that reduction targeted is through RNase H-mediated cleavage. One oligonucleotide, however, was effective at inhibiting levels as a 2'-O-methyl concentrations 2-3-fold greater than its phosphorothioate/deoxy homolog. results suggest ability to serve an H substrate, although not required for all oligonucleotides, certainly increases their potency. been used examine role played by mediating phorbol ester-induced changes cell adhesion molecule ICAM-1. In A549 cells, ICAM-1 increased 10-20-fold treatment cells with ester 12-myristate 13-acetate. When are depleted oligonucleotide increase response 13-acetate greatly reduced, demonstrating plays major this process.