title: Gastrin Enhances Autophagy and Promotes Gastric Carcinoma Proliferation via Inducing AMPKα.
abstract: Gastric cancer (GC) is one of the most frequent epithelial malignancies worldwide. The gastrointestinal (GI) peptide gastrin is an important regulator of the secretion and release of gastric acid from stomach parietal cells, and it also plays a vital role in the development and progression of GC. The aim of the current study was to investigate the role and underlying mechanism of gastrin and autophagy in regulating GC tumorigenesis. Gastrin-17 amide (G-17) was applied in the GC cell lines SGC7901 and MGC-803. The results showed that G-17 maintained the high viability of SGC7901 and MGC-803. The expression of autophagy marker proteins LC3II and Beclin1 was significantly increased, while the autophagy substrate p62 was obviously decreased in the gastrin group compared with the control group. Moreover, G-17 strengthened the expressions of AMPKα, Ras, Raf, MEK, and ERK1/2. Additionally, administration of AMPKα siRNA counteracted the effect of gastrin in SGC7901 cells. Finally, in an in vivo study of the tumor growth and survival rate of rats, the levels of AMPKα/Ras/Raf/MEK/ERK were significantly increased in the gastrin group and decreased following AMPKα shRNA injection. In conclusion, these findings indicate that gastrin plays a tumorigenic role by promoting autophagy in GC and may provide a novel therapeutic target for GC treatment.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Kun
authors.forename: Guo
authors.initials: G
authors.lastname: Hanqing
authors.forename: Tang
authors.initials: T
authors.lastname: Hailing
authors.forename: Yan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Zhang
authors.initials: Z
authors.lastname: Jun
authors.forename: Zhang
authors.initials: Z
authors.lastname: Lingxia
authors.forename: Han
authors.initials: H
authors.lastname: Kun
authors.forename: Zhang
authors.initials: Z
authors.lastname: Xin
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D005755:Gastrins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D005755:Gastrins; D055372:AMP-Activated Protein Kinases