title: Adenovirus-directed expression of TIPE2 suppresses gastric cancer growth via induction of apoptosis and inhibition of AKT and ERK1/2 signaling.
abstract: Tumor necrosis factor (TNF)-α-induced protein 8-like 2 (TNFAIP8L2/TIPE2) as a novel anti-inflammatory factor plays an important role in maintaining immune homeostasis. Recently, TIPE2 has been shown to inhibit hepatocarcinoma growth and metastasis through targeting Ras and Rac1. However, its effects in human cancers are poorly understood. In the present study, we analyzed TIPE2 mRNA expression in a panel of human gastric cancer cells (AGS, HGC-27 and SGC-7901) and then examined the cell-autonomous effects of adenovirus-mediated human TIPE2 gene transfer (AdVTIPE2) on AGS and HGC-27 human gastric cancer cells. We found that compared with the GES-1 normal human gastric mucous epithelial cells, human TIPE2 was lost in the AGS, HGC-27 and SGC-7901 gastric cancer cells. Adenovirus-mediated human TIPE2 overexpression significantly inhibited AGS and HGC-27 gastric cancer cell growth and induced AGS and HGC-27 tumor cell apoptosis in vitro. Furthermore, AdVTIPE2 treatment obviously suppressed the growth of AGS gastric cancer subcutaneously xenografted tumors implanted in athymic BALB/c nude mice in vivo. Mechanistically, AdVTIPE2 exhibited marked effects on the upregulation of Bax, cleaved Caspase-9, cleaved Caspase-3, cleaved poly ADP ribose polymerase as well as the downregulation of B-cell lymphoma (Bcl)-XL, phosphorylated-protein kinase B (p-PKB/AKT), phosphorylated-extracellular signal-regulated kinase 1/2 (p-ERK1/2) in AGS gastric cancer cells in vitro and in vivo. Collectively, AdVTIPE2 suppressed gastric cancer growth very possibly by the activation of intrinsic apoptotic pathway and the attenuation of AKT and ERK1/2 signaling. Thus, our data indicated that TIPE2 may be a novel potential therapeutic target for human gastric cancer.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: M
authors.initials: M
authors.lastname: Tao
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: C
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Oncology, Suzhou Xiangcheng People's Hospital, Suzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Cancer Research Unit, Saskatchewan Cancer Agency, Saskatoon, Saskatchewan, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xie
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D023061:Gene Order; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D020935:MAP Kinase Signaling System; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D014161:Transduction, Genetic; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C552057:TNFAIP8L2 protein, human; D051057:Proto-Oncogene Proteins c-akt