Department of Surgery, University of Melbourne, Austin Health, Lance Townsend Building, Lvl 8, Studley Road, Heidelberg, Victoria, Australia 3084.
Peptides. 2013 Aug;46:83-93. doi: 10.1016/j.peptides.2013.05.009. Epub 2013 Jun 3.
Progastrin (PG) is processed into a number of smaller peptides including amidated gastrin (Gamide), non-amidated glycine-extended gastrin (Ggly) and the C-terminal flanking peptide (CTFP). Several groups have reported that PG, Gamide and Ggly are biologically active in vitro and in vivo, and are involved in the development of gastrointestinal cancers. CTFP is bioactive in vitro but little is known of its effects in vivo. This study investigated the bioactivity of CTFP in vivo in normal tissues using gastrin deficient (GASKO) mice and in two mouse models of cancer (SCID mice bearing xenograft tumors expressing normal or knocked-down levels of gastrin and a mouse model of hepatic metastasis). As with Ggly, CTFP treatment stimulated colonic proliferation in GASKO mice compared to control. CTFP also significantly increased apoptosis in the gastric mucosa of male GASKO mice. CTFP did not appear to effect xenograft growth or the incidence of liver metastases. This is the first demonstration that CTFP has specific biological activity in vivo in the colon and stomach.
胃泌素（PG）被加工成多种较小的肽，包括酰胺化胃泌素（Gamide）、非酰胺化甘氨酰延伸胃泌素（Ggly）和 C 端侧翼肽（CTFP）。有几个研究小组报告称，PG、Gamide 和 Ggly 在体外和体内均具有生物活性，并且参与了胃肠道癌症的发展。CTFP 在体外具有生物活性，但对其体内作用知之甚少。本研究使用胃泌素缺乏（GASKO）小鼠以及两种癌症小鼠模型（表达正常或敲低水平胃泌素的 SCID 小鼠异种移植肿瘤和肝转移小鼠模型）研究了 CTFP 在正常组织中的体内生物活性。与 Ggly 一样，与对照组相比，CTFP 处理可刺激 GASKO 小鼠结肠增殖。CTFP 还显著增加了雄性 GASKO 小鼠胃黏膜的细胞凋亡。CTFP 似乎对异种移植物生长或肝转移的发生率没有影响。这是首次证明 CTFP 在体内对结肠和胃具有特定的生物学活性。
