title: ERK1/2 inhibition enhances apoptosis induced by JAK2 silencing in human gastric cancer SGC7901 cells.
abstract: Recent studies suggest JAK2 signaling may be a therapeutic target for treatment of gastric cancer (GC). However, the exact roles of JAK2 in gastric carcinogenesis are not very clear. Here, we have targeted JAK2 to be silenced by shRNA and investigated the biological functions and related mechanisms of JAK2 in GC cell SGC7901. In this study, JAK2 is commonly highly expressed in GC tissues as compared to their adjacent normal tissues (n = 75, p < 0.01). Specific down-regulation of JAK2 suppressed cell proliferation and colony-forming units, induced G2/M arrest in SGC7901 cells, but had no significant effect on cell apoptosis in vitro or tumor growth inhibition in vivo. Interestingly, JAK2 silencing-induced activation of ERK1/2, and inactivation of ERK1/2 using the specific ERK inhibitor PD98059 markedly enhanced JAK2 shRNA-induced cell proliferation inhibition, cell cycle arrest and apoptosis. Ultimately, combination of PD98059 and JAK2 shRNA significantly inhibited tumor growth in nude mice. Our results implicate JAK2 silencing-induced cell proliferation inhibition, cell cycle arrest, and ERK1/2 inhibition could enhance apoptosis induced by JAK2 silencing in SGC7901 cells.
authors.affiliation: Institute of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, Zhejiang, People's Republic of China.
authors.forename: Cuijuan
authors.initials: C
authors.lastname: Qian
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.forename: Jiji
authors.initials: J
authors.lastname: Wang
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.forename: Meng
authors.initials: M
authors.lastname: Xue
authors.forename: Tianhua
authors.initials: T
authors.lastname: Zhou
authors.forename: Weili
authors.initials: W
authors.lastname: Liu
authors.forename: Jianmin
authors.initials: J
authors.lastname: Si
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D059565:G2 Phase Cell Cycle Checkpoints; D055785:Gene Knockdown Techniques; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008819:Mice, Nude; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D005419:Flavonoids; D034741:RNA, Small Interfering; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one