J Korean Surg Soc.  2003 Mar;64(3):194-200.

Protein Kinase C-delta Mediates Nitric Oxide- induced Proliferation of Gastric Cancer Cells, MKN-2

• Kim HH
• Park KJ
• Kwak JY

Abstract

PURPOSE
The purpose of this study was to investigate the effect of exogenous nitric oxide (NO) on the proliferation of gastric carcinoma cells and the signaling pathways that regulate these responses. METHODS: MKN-28 cells were obtained from the Korean Cell Line Bank (KCLB) and maintained in DMEM culture media. The effect of sodium nitroprusside (SNP), a NO donor, on the proliferation of a serum-starved gastric carcinoma cell line, MKN-28, was examined by [3H]thymidine incorporation. Western blot was performed to analyze the translocation of protein kinase C (PKC)-deltafrom the cytosol to the plasma membrane of the MKN-28 cells. RESULTS: The proliferation of MKN-28 cells was significantly increased by SNP. It was also found that the proliferation was significantly inhibited by the protein kinase A (PKA) inhibitor, KT5720, and the protein kinase G inhibitor (PKG), KT5823, in SNP-treated cells. The SNP-induced proliferation was also inhibited by the PKC-deltaspecific inhibitor, rottlerin (1mu), but was increased by the PKC-beta inhibitor, Go6976 (1muM). The amount of translocated PKC-deltaprotein in the plasma membrane from the cytosol increased time-dependently after treating the cells with SNP, suggesting that NO activates PKC-delta Anti-inflammatory drugs, including dexamethasone, aspirin, indomethacin, mephenamic acid, and acetaminophen inhibited the SNP-induced proliferation of the cells and blocked of PKC-deltaactivation. CONCLUSION: NO stimulates the proliferation of serum- starved gastric cancer cells. The NO-induced proliferation may be mediated by PKC-delta The inhibitory effect of anti-inflammatory drugs on cell proliferation may be related to the inhibition of PKC-deltaactivity.

Keyword

Gastric carcinoma; MKN-28 cell; Nitric oxide; Protein kinase C-delta

MeSH Terms

Acetaminophen
Aspirin
Blotting, Western
Cell Line
Cell Membrane
Cell Proliferation
Culture Media
Cyclic AMP-Dependent Protein Kinases
Cyclic GMP-Dependent Protein Kinases
Cytosol
Dexamethasone
Humans
Indomethacin
Nitric Oxide
Nitroprusside
Protein Kinase C
Protein Kinase C-delta*
Protein Kinases*
Stomach Neoplasms*
Tissue Donors
Acetaminophen
Aspirin
Culture Media
Cyclic AMP-Dependent Protein Kinases
Cyclic GMP-Dependent Protein Kinases
Dexamethasone
Indomethacin
Nitric Oxide
Nitroprusside
Protein Kinase C
Protein Kinase C-delta
Protein Kinases