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

自建立4-硝基喹啉1-氧化物诱导大鼠舌癌模型以来，我们一直积极开展血管性研究。这一次，我们使用血管生成抑制剂（5-DFUR、行动蛋白和抗整合素抗体）来比较它们对两种舌癌（A组：长出的具有环状或网状血管的肿瘤，B组：具有分支状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组肿瘤。这种趋势在长出的具有网状血管的肿瘤中尤为明显。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。当不使用这些抑制剂时，分支最终由供血血管形成，但当使用这些抑制剂时，分支的生长终止（分支形成小珠）。这些发现与各种抗癌药物的动物实验结果基本相似，但这些抑制剂比抗代谢药物更能抑制肿瘤生长。在未来，重要的是：通过联合使用抗癌药物和血管生成抑制剂来增强抗癌效果；改善对现有血管被破坏的肿瘤的药物输送。

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.