Effect of Angiogenesis Inhibitors on Tongue Carcinoma Induced by 4-Nitroquinoline 1-Oxide (4NQO) on Rats

自从我们建立了4-硝基喹啉1-氧化物诱导的大鼠舌癌模型以来，我们一直在积极进行血管分布的研究。这次，我们给药了血管生成抑制剂（5-DFUR、肌动蛋白和抗整合素抗体），以比较它们对两种类型舌癌（A组：具有环形或网状血管的增生肿瘤，和B组：具有分支样血管或破坏现有血管的肿瘤）生长的影响。各抑制剂对A组肿瘤生长的抑制作用均大于B组。这种趋势在具有网状血管的肿瘤中明显强烈。然而，没有一个肿瘤完全消失，肿瘤直径最大缩小70%。我们通过扫描显微镜或血管模板分析检查了肿瘤血管的变化，发现肿瘤生长尖端的肿瘤血管形成珠子，并且狭窄。当不给予这些抑制剂时，最终从营养血管形成分支，但当给予这些抑制剂时，分支的生长终止（分支形成珠）。这些发现大多与各种抗癌药物的动物研究结果相似，但这些抑制剂比抗代谢药物更能抑制肿瘤生长。在未来，这将是重要的：增强抗癌药物和血管生成抑制剂的共同管理的抗癌效果，并改善药物输送到肿瘤中，现有的血管已被破坏。

Ever since we established 4-nitroquinoline 1-oxide-induced rat tongue cancer models, we have been actively conducting research on vascularity. This time, we administered angiogenesis inhibitors (5-DFUR, actinon, and anti-integrin antibody) to compare their effects on the growth of two types of tongue cancer (Group A : outgrowing tumors having ring-shaped or reticulated vessels, and Group B : tumors that have branch-like vessels or destroy existing vessels). Every inhibitor suppressed the growth of Group A tumors more than that of Group B tumors. This tendency was markedly strong for outgrowing tumors with reticulated vessels. However, none of the tumors completely disappeared, and the maximum tumor diameter reduction was 70%. We examined changes in tumor vessels by scanning microscopy or vessel template analysis, and found that tumor vessels at the tip of tumor growth formed beads and were narrow. When these inhibitors were not administered, branches eventually formed from feeding vessels, but when these inhibitors were administered, the growth of branches was terminated (branches formed beads). These findings were mostly similar to the results of animal studies on various anticancer drugs, but these inhibitors suppressed tumor growth more than antimetabolic agents. In the future, it will be important to : enhance anticancer effects by coadministering anticancer agents and angiogenesis inhibitors ; and improve drug delivery to tumors in which existing blood vessels have been destroyed.