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KMID : 0371320030640030194
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Journal of the Korean Surgical Society
2003 Volume.64 No. 3 p.194 ~ p.200
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Protein Kinase C-δ Mediates Nitric Oxide-induced Proliferation of Gastric Cancer Cells, MKN-28
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Kim Hyung-Ho
Park Ki-Jae
Kwak Jong-Young
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Abstract
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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 [(3)H]thymidine incorporation. Western blot was performed to analyze the translocation of protein kinase C (PKC)-delta from 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-delta specific inhibitor,
rottlerin (1 micro m), but was increased by the PKC-beta inhibitor, Go6976 (1 micro m). The amount of translocated PKC-delta protein 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-delta activation.
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-delta activity.
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KEYWORD
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Gastric carcinoma, MKN-28 cell, Nitric oxide, Protein kinase C-delta
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