Overexpression of protein kinase C-beta 1 isoenzyme suppresses indomethacin-induced apoptosis in gastric epithelial cells

Background & Aims: We have previously reported that nonsteroidal anti-infla mmatory drugs (NSAIDs) could induce apoptosis of gastric epithelial cells b oth in vivo and in vitro. This study investigated the role of protein kinas e C (PKC) isoforms in the regulation of NSAID-induced apoptosis, Methods: P rotein levels of 12 PKC isoforms in:AGS cells, in the presence or absence o f indomethacin, were determined by Western blot, The effect of PKC-beta 1 o verexpression by transfection with its complementary DNA (cDNA) on indometh acin-induced apoptosis and apoptosis-related genes, including p53, p21(waf1 cip1), and c-myc, was further investigated, Results: Treatment with indomet hacin decreased the abundance of PKC-beta 1 and increased that of PKC-beta 2, eta, and epsilon, but did not alter the expression of PKC alpha, gamma, zeta, delta, iota, and mu. Overexpression of PKC-beta 1 attenuated the apop totic response of AGS cells to indomethacin, associated with overexpression of p21(waf1/cip1) in both messenger RNA and protein levels. Inhibition of PKC-beta 1-mediated overexpression of p21(waf1/cip1) by its antisense cDNA partially reduced the antiapoptotic effect of PKC-beta 1. Conclusions: Indo methacin-induced apoptosis in gastric cancer cells is partly mediated by di fferential regulation of PKC isoform expression, Enhanced expression of exo genous PKC-beta 1 protects against indomethacin-induced apoptosis through u pregulation of p21(waf1/cip1).