Abstract
Gastrin, cholecystokinin2 receptor (CCK2R), and cyclooxygenase-2 (COX-2) have been implicated in the carcinogenesis and progression of gastric cancer. Our study demonstrated that antagonist or siRNA against CCK2R blocked amidated gastrin (G17)-induced activation of STAT3 and Akt in gastric cancer cell lines. G17-increased COX-2 expression and cell proliferation were effectively blocked by CCK2R antagonist and inhibitors of JAK2 and PI3K. In addition, knockdown of STAT3 expression significantly attenuated G17-induced PI3K/Akt activation, COX-2 expression, and cell proliferation. These results suggest that CCK2R-mediated COX-2 up-regulation via JAK2/STAT3/PI3K/Akt pathway is involved in the proliferative effect of G17 on human gastric cancer cells.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line, Tumor
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Cell Proliferation
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Cyclooxygenase 2 / metabolism*
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Gastrins / metabolism*
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Humans
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Janus Kinase 2 / antagonists & inhibitors
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Janus Kinase 2 / metabolism*
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Phosphatidylinositol 3-Kinase / metabolism*
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Phosphoinositide-3 Kinase Inhibitors
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Phosphorylation
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Protein Kinase Inhibitors / pharmacology
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Proto-Oncogene Proteins c-akt / metabolism*
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RNA Interference
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RNA, Messenger / metabolism
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Receptor, Cholecystokinin B / antagonists & inhibitors
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Receptor, Cholecystokinin B / genetics
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Receptor, Cholecystokinin B / metabolism*
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STAT3 Transcription Factor / genetics
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STAT3 Transcription Factor / metabolism*
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Signal Transduction
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Stomach Neoplasms / enzymology*
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Stomach Neoplasms / genetics
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Stomach Neoplasms / pathology
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Time Factors
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Transfection
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Up-Regulation
Substances
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Gastrins
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Phosphoinositide-3 Kinase Inhibitors
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Protein Kinase Inhibitors
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RNA, Messenger
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Receptor, Cholecystokinin B
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STAT3 Transcription Factor
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STAT3 protein, human
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Cyclooxygenase 2
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PTGS2 protein, human
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Phosphatidylinositol 3-Kinase
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JAK2 protein, human
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Janus Kinase 2
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Proto-Oncogene Proteins c-akt