Nitric Oxide에 의한 위암 세포 MKN-28의 증식에 대한 Protein Kinase C-delta의 매개 역할
Protein Kinase C-δ Mediates Nitric Oxide-induced Proliferation of Gastric Cancer Cells, MKN-28
김형호, 박기재, 곽종영,
소속 상세정보
김형호 ( Kim Hyung-Ho )
동아대학교 의과대학 외과학교실
박기재 ( Park Ki-Jae )
동아대학교 의과대학 외과학교실
곽종영 ( Kwak Jong-Young )
동아대학교 의과대학 생화학교실
KMID : 0371320030640030194
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 [(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.
키워드
위암;MKN-28 세포;산화질소;단백질인산화 효소 C-δ
Gastric carcinoma;MKN-28 cell;Nitric oxide;Protein kinase C-delta
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