Konno H, Tanaka T, Matsuda I, Kanai T, Maruo Y, Nishino N, Nakamura S, Baba S
Second Department of Surgery, Hamamatsu University School of Medicine, Japan.
Int J Cancer. 1995 Apr 10;61(2):268-71. doi: 10.1002/ijc.2910610221.
Angiogenesis inhibitors have attracted considerable interest. The anti-tumor and anti-metastatic effects of TNP-470, an angiogenesis inhibitor, and mitomycin C (MMC), a representative anti-neoplastic agent, were investigated using a xenotransplanted human colon cancer, TK-4. Suturing of small pieces of TK-4 tumors to the cecal wall in nude mice (orthotopic transplantation) induced liver metastasis. Mice were randomly divided into 3 groups; a control group given saline solution, a group receiving TNP-470 and a group receiving MMC. TNP-470 was given s.c. on alternate days for 5 weeks from day 10 after cecal transplantation and MMC was administered intraperitoneally (i.p.) once a week from day 10 after cecal transplantation. MMC significantly inhibited cecal tumor growth. In the control group, liver metastases developed in 9 out of 10 mice, including 3 with more than 20 metastatic foci. Liver metastasis also developed in 8 out of 10 mice receiving MMC, 2 of which had many metastases. In contrast, liver metastasis developed in only 2 out of 8 mice in the TNP-470 group and neither of these animals had numerous metastases.
血管生成抑制剂已引起了相当大的关注。使用人结肠癌异种移植瘤TK-4研究了血管生成抑制剂TNP-470和代表性抗肿瘤药物丝裂霉素C（MMC）的抗肿瘤和抗转移作用。将小块TK-4肿瘤缝合到裸鼠的盲肠壁上（原位移植）可诱导肝转移。将小鼠随机分为3组：给予生理盐水的对照组、接受TNP-470的组和接受MMC的组。从盲肠移植后第10天起，每隔一天皮下注射TNP-470，持续5周；从盲肠移植后第10天起，每周腹腔注射一次MMC。MMC显著抑制盲肠肿瘤生长。在对照组中，10只小鼠中有9只发生肝转移，其中3只转移灶超过20个。接受MMC的10只小鼠中有8只也发生了肝转移，其中2只转移灶较多。相比之下，TNP-470组的8只小鼠中只有2只发生肝转移，且这两只动物均无大量转移灶。
