Overexpression of protein kinase C-beta1 isoenzyme suppresses indomethacin-induced apoptosis in gastric epithelial cells

Gastroenterology. 2000 Mar;118(3):507-14. doi: 10.1016/s0016-5085(00)70256-3.


Background & aims: We have previously reported that nonsteroidal anti-inflammatory drugs (NSAIDs) could induce apoptosis of gastric epithelial cells both in vivo and in vitro. This study investigated the role of protein kinase C (PKC) isoforms in the regulation of NSAID-induced apoptosis.

Methods: Protein levels of 12 PKC isoforms in AGS cells, in the presence or absence of indomethacin, were determined by Western blot. The effect of PKC-beta1 overexpression by transfection with its complementary DNA (cDNA) on indomethacin-induced apoptosis and apoptosis-related genes, including p53, p21(waf1/cip1), and c-myc, was further investigated.

Results: Treatment with indomethacin decreased the abundance of PKC-beta1 and increased that of PKC-beta2, eta, and epsilon, but did not alter the expression of PKC alpha, gamma, zeta, delta, iota, and micro. Overexpression of PKC-beta1 attenuated the apoptotic response of AGS cells to indomethacin, associated with overexpression of p21(waf1/cip1) in both messenger RNA and protein levels. Inhibition of PKC-beta1-mediated overexpression of p21(waf1/cip1) by its antisense cDNA partially reduced the antiapoptotic effect of PKC-beta1.

Conclusions: Indomethacin-induced apoptosis in gastric cancer cells is partly mediated by differential regulation of PKC isoform expression. Enhanced expression of exogenous PKC-beta1 protects against indomethacin-induced apoptosis through up-regulation of p21(waf1/cip1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antisense Elements (Genetics) / pharmacology
  • Apoptosis / drug effects*
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / genetics
  • Cyclins / metabolism
  • DNA, Complementary / pharmacology
  • Gastric Mucosa / enzymology*
  • Gastric Mucosa / pathology
  • Gastric Mucosa / physiopathology*
  • Indomethacin / pharmacology*
  • Isoenzymes / metabolism*
  • Protein Kinase C / metabolism*
  • Protein Kinase C beta
  • Proto-Oncogene Proteins c-myc / metabolism
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / metabolism


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antisense Elements (Genetics)
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA, Complementary
  • Isoenzymes
  • Proto-Oncogene Proteins c-myc
  • Tumor Suppressor Protein p53
  • Protein Kinase C
  • Protein Kinase C beta
  • Indomethacin