Smith Jill P, Nadella Sandeep, Osborne Nick
Department of Medicine, Georgetown University, Washington, District of Columbia.
Cato Research, Durham, North Carolina.
Cell Mol Gastroenterol Hepatol. 2017 Mar 14;4(1):75-83. doi: 10.1016/j.jcmgh.2017.03.004. eCollection 2017 Jul.
Gastric cancer is the third leading cause of cancer-related mortality worldwide. Despite progress in understanding its development, challenges with treatment remain. Gastrin, a peptide hormone, is trophic for normal gastrointestinal epithelium. Gastrin also has been shown to play an important role in the stimulation of growth of several gastrointestinal cancers including gastric cancer. We sought to review the role of gastrin and its pathway in gastric cancer and its potential as a therapeutic target in the management of gastric cancer. In the normal adult stomach, gastrin is synthesized in the G cells of the antrum; however, gastrin expression also is found in many gastric adenocarcinomas of the stomach corpus. Gastrin's actions are mediated through the G-protein-coupled receptor cholecystokinin-B (CCK-B) on parietal and enterochromaffin cells of the gastric body. Gastrin blood levels are increased in subjects with type A atrophic gastritis and in those taking high doses of daily proton pump inhibitors for acid reflux disease. In experimental models, proton pump inhibitor-induced hypergastrinemia and infection with increase the risk of gastric cancer. Understanding the gastrin:CCK-B signaling pathway has led to therapeutic strategies to treat gastric cancer by either targeting the CCK-B receptor with small-molecule antagonists or targeting the peptide with immune-based therapies. In this review, we discuss the role of gastrin in gastric adenocarcinoma, and strategies to block its effects to treat those with unresectable gastric cancer.
胃癌是全球癌症相关死亡的第三大主要原因。尽管在了解其发展方面取得了进展，但治疗方面仍存在挑战。胃泌素是一种肽类激素，对正常胃肠道上皮具有营养作用。胃泌素还被证明在刺激包括胃癌在内的几种胃肠道癌症的生长中起重要作用。我们试图综述胃泌素及其信号通路在胃癌中的作用，以及其作为胃癌治疗靶点的潜力。在正常成年胃中，胃泌素在胃窦的G细胞中合成；然而，在许多胃体部胃腺癌中也发现了胃泌素的表达。胃泌素的作用是通过胃体壁细胞和肠嗜铬细胞上的G蛋白偶联受体胆囊收缩素B（CCK-B）介导的。A型萎缩性胃炎患者以及因胃酸反流疾病每日服用高剂量质子泵抑制剂的患者，其胃泌素血水平会升高。在实验模型中，质子泵抑制剂诱导的高胃泌素血症和幽门螺杆菌感染会增加患胃癌的风险。对胃泌素：CCK-B信号通路的了解已经产生了通过用小分子拮抗剂靶向CCK-B受体或用基于免疫的疗法靶向该肽来治疗胃癌的策略。在这篇综述中，我们讨论了胃泌素在胃腺癌中的作用，以及阻断其作用以治疗不可切除胃癌患者的策略。
