Bruns Helge, Kazanavicius Darius, Schultze Daniel, Saeedi Mohammed Al, Yamanaka Kenia, Strupas Kestutis, Schemmer Peter
Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.
Center of Abdominal Surgery, Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania.
Amino Acids. 2016 Nov;48(11):2549-2558. doi: 10.1007/s00726-016-2278-0. Epub 2016 Jun 28.
Neo-angiogenesis is important for tumor growth. Glycine is a non-toxic amino acid with suspected anti-angiogenic effects. This study was designed to evaluate anti-angiogenic effects of glycine in colorectal cancer. Glycine was added to cultures of human and rat colorectal cancer cells (CRC), and endothelial cells (HUVEC). Glycine's direct impact was monitored using MTT assays. Angiogenesis in HUVEC was monitored using 3D sprouting and migration assays. VEGF and CRC-conditioned media were used to stimulate angiogenesis. The glycine receptor (GlyR) was detected using Western blotting and inhibited using strychnine. The WAG-Rij/CC-531 model of metastatic CRC was used to evaluate glycine's impact in vivo. Tumor growth and vessel density were monitored in rats fed with or without 5 % glycine for 14 days. VEGF and conditioned media significantly increased proliferation, migration, and capillary formation to up to 267 %. Glycine completely neutralized this effect and strychnine completely blunted glycine's effect. GlyR was detected in HUVEC. Tumor volume, weight, and vessel density decreased by 35 % (p = 0.02), 34 % (p = 0.03), and 55 % (p = 0.04) in glycine-fed animals. Glycine inhibits angiogenic signaling of endothelial cells and tumor growth. Glycine would be a promising additive to standard and targeted cancer therapies.
新生血管形成对肿瘤生长至关重要。甘氨酸是一种无毒氨基酸，具有潜在的抗血管生成作用。本研究旨在评估甘氨酸在结直肠癌中的抗血管生成作用。将甘氨酸添加到人及大鼠结肠癌细胞（CRC）和内皮细胞（HUVEC）的培养物中。使用MTT法监测甘氨酸的直接影响。使用三维发芽和迁移试验监测HUVEC中的血管生成。使用VEGF和CRC条件培养基刺激血管生成。使用蛋白质印迹法检测甘氨酸受体（GlyR），并使用士的宁进行抑制。使用转移性CRC的WAG-Rij/CC-531模型评估甘氨酸在体内的影响。在喂食或未喂食5%甘氨酸14天的大鼠中监测肿瘤生长和血管密度。VEGF和条件培养基显著增加增殖、迁移和毛细血管形成，增幅高达267%。甘氨酸完全中和了这种作用，士的宁完全消除了甘氨酸的作用。在HUVEC中检测到GlyR。喂食甘氨酸的动物的肿瘤体积、重量和血管密度分别下降了35%（p = 0.02）、34%（p = 0.03）和55%（p = 0.04）。甘氨酸抑制内皮细胞的血管生成信号和肿瘤生长。甘氨酸有望成为标准和靶向癌症治疗的添加剂。
