Inhibitory effect of the angiogenesis inhibitor TNP-470 on hepatocellular carcinomas

血管生成抑制剂TNP-470对肝细胞癌的抑制作用

基本信息

批准号：
07670634
负责人：
TORIMURA Takuji
金额：
$ 1.22万
依托单位：
Kurume University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670634/
关键词：
hepatocellular carcinoma inhibition of angiogenesis TNP-470 肺転移抑制

项目摘要

We performed the following studies to clarify the inhibitory effect of angiogenesis inhibitor, TNP-470 on the growth of hepatocellular carcinomas.1. Studies using hepatocellular carcinomas induced by a choline-deficient L-amino acid defined (CDAA) diet in rats. Hepatocellular carcinomas usually begin to develop from 6 to 12 months after the beginning of CDAA diet. Rats were classified into 4 groups : Group A,the rats which were injected with TNP-470 from 7 months to 1 year old ; Group B,the rats which were injected with saline from 7 months to 1 year old ; Group C,the rats which were injected with TNP-470 for 4 months from 1 year old ; Group D,the rats which were injected with saline for 4 months from 1 year old.1) The incidence and size of preneoplastic lesions were not different between four groups. While, the incidence and size of hepatocellular carcinoma in Group A significantly decreased in comparison with group B.Those in Group C also decreased in comparison with Group D.2) Although TNP-470 caused severe weight loss in treated rats, the histology of liver cirrhosis and liver function were not influenced.3) The preliferation of hepatocellular carcinoma was not different between four groups. The apoptotic ratio of hepatoma cells in Group A and Group C was higher than that in Group B and Group D.The vascularity in hepatocellular carcinoma in Group A and Group C tended to be decreased in comparison with that in Group B and Group D.2. in vitro studiesThe proliferation of human endothelial cells cultured with hepatoma cells was faster than those cells cultured without hepatoma cells. Although the proliferation of human endothelial cells was inhibited by the addition of TNP-470, hepatoma cells were not inhibited. These findings suggests that the inhibition of angiogenesis may suppress the growth of hepatocellular carcinoma.

我们进行了以下研究，以阐明血管生成抑制剂TNP-470对肝细胞癌生长的抑制作用。1。使用大鼠中胆碱缺陷的L-氨基酸（CDAA）饮食诱导的肝细胞癌的研究。 CDAA饮食开始后的6个月至12个月，肝细胞癌通常开始发展。将大鼠分为4组：A组，从7个月到1岁的TNP-470注射的大鼠； B组，从7个月到1岁的盐水注射的大鼠； C组，从1岁开始注射TNP-470的大鼠4个月； D组，从1岁开始注射盐水4个月的大鼠。1）四组之间的发生率和大小的肿瘤病变的发病率和大小没有差异。而与B组B相比，A组A组的肝细胞癌的发生率和大小显着降低，但与第of组相比，C组的发生率也有所下降，尽管TNP-470引起了治疗大鼠的严重体重减轻，肝脏cirrhosis和肝脏功能的组织学不受影响。 A组和C组中肝癌细胞的凋亡比高于B组和D组。与B组和B组D.2相比，A组和C组的肝细胞癌的血管性趋于降低。用肝瘤细胞培养的人内皮细胞的体外牙齿增殖比没有肝癌细胞培养的细胞更快。尽管通过添加TNP-470抑制了人内皮细胞的增殖，但并未抑制肝癌细胞。这些发现表明，血管生成的抑制可能抑制肝细胞癌的生长。