title: CXCR1 promotes malignant behavior of gastric cancer cells in vitro and in vivo in AKT and ERK1/2 phosphorylation.
abstract: CXCR1 is a member of the chemokine receptor family, which was reported to play an important role in several cancers. The present study investigated the influence of CXCR1 stable knockdown or overexpression on the malignant behavior of gastric cancer cells in vitro and in vivo and the potential mechanisms. MKN45 and BGC823 cells were stably transfected with plasmid pYr-1.1-CXCR1-shRNA (knockdown) and pIRES2-ZsGreen1-CXCR1 (overexpression), respectively. Malignant behavior was evaluated in vitro for changes in proliferation by MTT and colony forming assays; cell cycle and apoptosis by flow cytometry; and migration and invasion using transwell and wound-healing assays. Proliferation, cell cycle, apoptosis, migration and invasion-related signaling molecule expression were measured by real-time RT-PCR and western blot analysis. CXCR1 knockdown and overexpressing xenografts were monitored for in vivo tumor growth. Stable knockdown of CXCR1 inhibited MKN45 cell proliferation, migration and invasion, but were reversed in BGC823 cells stably overexpressing CXCR1. In addition, MKN45 cells stably transfected with CXCR1 shRNA inhibited AKT and ERK1/2 phosphorylation, protein expression of cyclin D1, EGFR, VEGF, MMP-9, MMP-2 and Bcl-2, and increased protein expression of Bax and E-cadherin (all P<0.05). In vivo CXCR1-shRNA-MKN45 cells transplanted into nude mice formed smaller tumors than non-transfected or scrambled-shRNA cells (both P<0.05). In contrast BGC823 cells overexpressing CXCR1 formed larger tumors in mice than cells carrying an empty expression plasmid or non-transfected cells (both P<0.05). CXCR1 promoted gastric cancer cell proliferation, migration and invasion. The present study provides preclinical data to support CXCR1 as a novel therapeutic target for gastric cancer.
authors.affiliation: Department of Pathology, Xiang-ya Hospital, Central South University, Changsha, Hunan 410083, P.R. China.
authors.forename: Junpu
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, School of Basic Medicine, Central South University, Changsha, Hunan 410083, P.R. China.
authors.forename: Wanming
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Pathology, Xiang-ya Hospital, Central South University, Changsha, Hunan 410083, P.R. China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pathology, Xiang-ya Hospital, Central South University, Changsha, Hunan 410083, P.R. China.
authors.forename: Kuansong
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Neurology, Third Xiang-ya Hospital, Central South University, Changsha, Hunan 410083, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Pathology, Xiang-ya Hospital, Central South University, Changsha, Hunan 410083, P.R. China.
authors.forename: Baihua
authors.initials: B
authors.lastname: Luo
authors.affiliation: Department of Pathology, Xiang-ya Hospital, Central South University, Changsha, Hunan 410083, P.R. China.
authors.forename: Gengqiu
authors.initials: G
authors.lastname: Luo
authors.affiliation: Department of Pathology, School of Basic Medicine, Central South University, Changsha, Hunan 410083, P.R. China.
authors.forename: Weiyuan
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pathology, School of Basic Medicine, Central South University, Changsha, Hunan 410083, P.R. China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathology, Xiang-ya Hospital, Central South University, Changsha, Hunan 410083, P.R. China.
authors.forename: Jinghe
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology, Xiang-ya Hospital, Central South University, Changsha, Hunan 410083, P.R. China.
authors.forename: Jifang
authors.initials: J
authors.lastname: Wen
mesh_terms: D000818:Animals; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System; D051379:Mice; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D023062:Receptors, Interleukin-8A / Q000235:genetics* / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D023062:Receptors, Interleukin-8A; D051057:Proto-Oncogene Proteins c-akt