Prevention of hepatic metastasis of human colon cancer by angiogenesis inhibitor TNP-470.
Prevention of hepatic metastasis of human colon cancer by angiogenesis inhibitor TNP-470.
复制标题
血管生成抑制剂 TNP-470 预防人结肠癌肝转移。
作者：
Tatsuo Tanaka;Hiroyuki Konno;I. Matsuda;Satoshi Nakamura;S. Baba
本文研究了一种有效的血管生成抑制剂O-（氯乙酰氨基甲酰基）烟曲霉醇（TNP-470）在人结肠癌裸鼠移植瘤中的抗转移作用。将来自三种已建立的人结肠癌细胞系（TK-3、TK-4和TK-9）的小块肿瘤（其维持在裸鼠中）通过浆膜中的小切口植入裸鼠的盲肠壁中。TNP-470（20或30 mg/kg）皮下给药。从植入后第10天开始每隔一天注射一次，6周后处死小鼠。植入肿瘤的重量无差异（对照组：0.45 +/- 0.29 g，治疗组：0.49 +/- 0.27 g）。TNP-470的抗转移作用以剂量依赖性方式清楚地证明。在给予20 mg/kg TNP-470的小鼠中，10例病例中有3例发生肝转移。在30 mg/kg剂量组中，17只小鼠中仅1只发生转移，而对照组32只小鼠中有22只发生转移。治疗组的转移灶数量显著较少。然而，TNP-470有效地防止了肝转移，但对原发肿瘤的生长没有影响。这些结果表明，血管生成抑制剂TNP-470对人结肠癌的体内肝转移具有很强的抑制活性。
The antimetastatic effect of a potent angiogenesis inhibitor, O-(chloroacetyl-carbamoyl)fumagillol (TNP-470), was investigated in nude mice implanted with human colon cancer. Small pieces of tumors from three established human colon cancer cell lines (TK-3, TK-4, and TK-9), which were maintained in nude mice, were implanted into the cecal wall of nude mice via a small incision in the serosa. TNP-470 (20 or 30 mg/kg) was given s.c. every other day from day 10 after implantation, and the mice were sacrificed after 6 weeks. There was no difference in the weight of the implanted tumors (control group: 0.45 +/- 0.29 g versus treated group: 0.49 +/- 0.27 g). An antimetastatic effect of TNP-470 was clearly demonstrated in a dose-dependent manner. In the mice given 20 mg/kg TNP-470, liver metastasis developed in 3 of 10 cases. In the 30-mg/kg group, metastasis developed in only 1 of 17 mice, while it developed in 22 of 32 mice of the control group. The number of metastatic foci was significantly less in the treated groups. TNP-470 effectively prevented liver metastasis, however, but had no effect on the growth of the primary tumor. These results indicate that the angiogenesis inhibitor TNP-470 has a strong inhibitory activity against in vivo hepatic metastasis of human colon cancer.