Masur K, Schwartz F, Entschladen F, Niggemann B, Zaenker K S
Institute of Immunology, Witten/Herdecke University, Stockumer Str. 10, 58448 Witten, Germany.
Regul Pept. 2006 Dec 10;137(3):147-55. doi: 10.1016/j.regpep.2006.07.003. Epub 2006 Aug 14.
The glucagon-like peptides-1 and -2 (GLP-1 and -2) are co-secreted after food intake from intestinal L cells. Since both peptides are rapidly degraded by dipeptidyl peptidase-IV (DPPIV), research is focused on the development of DPPIV inhibitors or DPPIV resistant.
In this study we investigated, whether the inhibition of DPPIV activity and the resulting increased half-life of DPPIV substrates may influence cancer development and progression.
We examined proliferation and migratory activity of two human colon cancer cell lines (SW480, HT29) after stimulation with GLP-2 in combination with or without DPPIV inhibitors.
Migratory activity was increased by 25% from 20% matrix induced activity to a maximum of 45% (100 nM GLP-2). In cells expressing CD26, migration was prolonged by addition of DPPIV inhibitors in a concentration dependent manner. After treatment with GLP-2 doubling time decreased from 2.4 to 1.5 days - and addition of DPPIV inhibitors enhanced the effect of GLP-2.
The use of DPPIV inhibitors together with GLP-2 led to increased proliferation as well as elevated migratory activity. Therefore, the use of DPPIV inhibitors could increase the risk of promoting an already existing intestinal tumour and may support the potential of colon cancer cells to metastasize.
进食后，胰高血糖素样肽-1和-2（GLP-1和GLP-2）由肠道L细胞共同分泌。由于这两种肽都会被二肽基肽酶-IV（DPPIV）迅速降解，因此研究重点在于开发DPPIV抑制剂或抗DPPIV的药物。
在本研究中，我们调查了抑制DPPIV活性以及由此导致的DPPIV底物半衰期延长是否会影响癌症的发生和发展。
我们检测了两种人结肠癌细胞系（SW480、HT29）在有或没有DPPIV抑制剂的情况下，用GLP-2刺激后的增殖和迁移活性。
迁移活性从20%的基质诱导活性增加了25%，最高达到45%（100 nM GLP-2）。在表达CD26的细胞中，添加DPPIV抑制剂可使迁移时间以浓度依赖的方式延长。用GLP-2处理后，倍增时间从2.4天降至1.5天，添加DPPIV抑制剂可增强GLP-2的作用。
DPPIV抑制剂与GLP-2联合使用会导致增殖增加以及迁移活性升高。因此，使用DPPIV抑制剂可能会增加促进已存在的肠道肿瘤发展的风险，并可能增强结肠癌细胞转移的可能性。
