Maeda M, Ligo M, Tsuda H, Fujita H, Yonemura Y, Nakagawa K, Endo Y, Sasaki T
Experimental Pathology and Chemotherapy Division, National Cancer Center Research Institute, Tokyo, Japan.
Anticancer Drug Des. 2000 Jun;15(3):217-23.
The therapeutic potential of a diaminotriazine, 2,4-diamino-6-(pyridine-4-yl)-1,3,5-triazine (4PyDAT), was investigated in a metastatic model using the mouse colon 26 carcinoma variant (Co26Lu), which preferentially metastasizes to the lung of mouse. The compound had a moderate antimetastatic activity as well as antitumor activity, without toxicity to the host, when administered orally. In the cytotoxicity test in vitro, 4PyDAT showed very weak direct cytotoxicity against the Co26Lu cell line, Co26Lu(F55) (IC50 < or = 1000 microM). Less microcapiral formation on tumors were observed for the treated group with a hemorrhage than the control group under microscopy. 4PyDAT significantly inhibited the production of urokinase-type plasminogen activator (u-PA) in Co26Lu(F55) cells. These results suggest that the antimetastatic and antitumor activities of 4PyDAT are due in part to inhibition of angiogenesis, rather than direct antiproliferative action on the tumor cells. 4PyDAT may become a lead compound to develop antitumor triazine derivatives based on antiangiogenic action.
使用优先转移至小鼠肺部的小鼠结肠26癌变体（Co26Lu），在转移模型中研究了二氨基三嗪2,4 - 二氨基 - 6 -（吡啶 - 4 - 基）-1,3,5 - 三嗪（4PyDAT）的治疗潜力。口服给药时，该化合物具有适度的抗转移活性以及抗肿瘤活性，且对宿主无毒性。在体外细胞毒性试验中，4PyDAT对Co26Lu细胞系Co26Lu(F55)表现出非常弱的直接细胞毒性（IC50≤1000微摩尔）。显微镜下观察发现，与对照组相比，治疗组肿瘤上形成的微毛细血管较少且有出血现象。4PyDAT显著抑制Co26Lu(F55)细胞中尿激酶型纤溶酶原激活剂（u - PA）的产生。这些结果表明，4PyDAT的抗转移和抗肿瘤活性部分归因于对血管生成的抑制，而非对肿瘤细胞的直接抗增殖作用。4PyDAT可能成为基于抗血管生成作用开发抗肿瘤三嗪衍生物的先导化合物。
