Oncol Res. 2017 Sep 21;25(8):1399-1407. doi: 10.3727/096504016X14823648620870. Epub 2017 Jan 5.
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.
胃癌（GC）是全球最常见的上皮恶性肿瘤之一。胃肠道（GI）肽胃泌素是胃酸从胃壁细胞分泌和释放的重要调节剂，它在 GC 的发生和发展中也起着至关重要的作用。本研究旨在探讨胃泌素和自噬在调节 GC 肿瘤发生中的作用和潜在机制。胃泌素-17 酰胺（G-17）应用于 GC 细胞系 SGC7901 和 MGC-803。结果表明，G-17 维持了 SGC7901 和 MGC-803 的高活力。与对照组相比，胃泌素组自噬标记蛋白 LC3II 和 Beclin1 的表达明显增加，而自噬底物 p62 明显减少。此外，G-17 增强了 AMPKα、Ras、Raf、MEK 和 ERK1/2 的表达。此外，用 AMPKα siRNA 处理可拮抗胃泌素对 SGC7901 细胞的作用。最后，在大鼠肿瘤生长和生存率的体内研究中，胃泌素组 AMPKα/Ras/Raf/MEK/ERK 水平明显升高，而 AMPKα shRNA 注射后则降低。总之，这些发现表明胃泌素通过促进 GC 中的自噬发挥致癌作用，可能为 GC 治疗提供新的治疗靶点。
