title: Gastrin acting on the cholecystokinin2 receptor induces cyclooxygenase-2 expression through JAK2/STAT3/PI3K/Akt pathway in human gastric cancer cells.
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.
authors: Department of Geriatric Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors: Wei
authors: W
authors: Xu
authors: Guo-Sheng
authors: GS
authors: Chen
authors: Yun
authors: Y
authors: Shao
authors: Xiao-Lin
authors: XL
authors: Li
authors: Hai-Chen
authors: HC
authors: Xu
authors: Hao
authors: H
authors: Zhang
authors: Guo-Qing
authors: GQ
authors: Zhu
authors: Yi-Chan
authors: YC
authors: Zhou
authors: Xiao-Pu
authors: XP
authors: He
authors: Wei-Hao
authors: WH
authors: Sun
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism*; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D043887:Receptor, Cholecystokinin B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: D005755:Gastrins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D043887:Receptor, Cholecystokinin B; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D058539:Phosphatidylinositol 3-Kinase; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D051057:Proto-Oncogene Proteins c-akt