Gene transfer of Endostatin and K1-5 suppresses the growth of hepatocellular carcinoma

内皮抑素和 K1-5 基因转移抑制肝细胞癌的生长

基本信息

批准号：
11670550
负责人：
TORIMURA Takuji
金额：
$ 2.37万
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：
1999
资助国家：
日本
起止时间：
1999 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670550/
关键词：
Gene therapy Endostatin K1-5 cDNA Damage of endothelial cell Liposome Hepatoma Nude mouse Kringle1-5 endostatin 内皮細胞遺伝子銃プラスミド PCR

项目摘要

We investigated anti-tumor effect of endostatin and K1-5, potent anti-angiogenc factors. We used KYN-2 cells, a human hepatoma cell line. KYN-2 cells(2 ×10^6 cells)were implanted in the liver of nude mice. Seven days after implantation, 100 μg of endostatin cDNA and K1-5 cDNA were transferred via tail vein by liposome method twice a week for 3weeks. For control mice, empty plasmid was injected. At day 28, the mice ware killed and tumor volume was calculated as length x width^2 × 0.52.Of endostatin treated group, tumor growth was not observed in 2 of 6 cases. Average tumor volume was 69.5 ± 76mm^3. Of K1-5 treated group, tumor growth was not observed in 3 of 6 cases. Average tumor volume was 69.5 ± 76mm^3. On the otherhand, tumor development was detected in every case of control group. Average tumor volume was 2175 ± 1386mm^3(p<0.05). The expression of endostatin and K1-5 proteins was detected in pulmonary epithelial cells, hepatocytes, and hapatoma cells, respectively.In addition, we investigated anti-tumor effect of adenovirus-mediated gene transfer of endostatin. Adenovirus-endostatin (1.5×10^9) was injected into the peritoneal cavity of nude mice 7days after implantation of KYN-2 cells (2 × 10^6 cells)into the liver. At day 28, mice ware killed and tumor volume was calculated. In endostatin treated group, average tumor volume was 180± 129mm^3. In control group, average tumor volume was 1797± 1228mm^3(p<0.05). These findings indicate that the gene therapy with endostatin and K1-5, potent anti-angiogenc factors significantly suppresses the growth of hepatocellular carcinoma.

我们研究了潜在的抗血管含量因素的内接抑制素和K1-5的抗肿瘤效应。我们使用了人类肝癌细胞系Kyn-2细胞。将Kyn-2细胞（2×10^6细胞）植入裸鼠的肝脏中。植入后7天，每周两次通过脂质体方法通过尾静脉转移100μg内骨cDNA和K1-5 cDNA，用于3周。对于对照小鼠，注入空质粒。在第28天，将鼠标杀死的小鼠和肿瘤体积计算为长度x宽度^2×0.52。在经抑素治疗的组中，在6例中没有观察到肿瘤的生长。平均肿瘤体积为69.5±76mm^3。在K1-5治疗组中，在6例中没有观察到肿瘤的生长。平均肿瘤体积为69.5±76mm^3。另一方面，在每个对照组的情况下都检测到肿瘤的发展。平均肿瘤体积为2175±1386mm^3（p <0.05）。分别在肺上皮细胞，肝细胞和Hapatoma细胞中检测到内抑素和K1-5蛋白的表达。此外，我们研究了腺病毒介导的内抑素基因转移的抗肿瘤作用。将Kyn-2细胞（2×10^6细胞）植入后，将腺病毒 - 内替汀（1.5×10^9）注入裸鼠的腹膜7天。 28，计算了杀死的小鼠塑料和肿瘤体积。在经抑素治疗组中，平均肿瘤体积为180±129mm^3。在对照组中，平均肿瘤体积为1797±1228mm^3（p <0.05）。这些发现表明，使用内接抑制素和K1-5的基因疗法潜在的抗血管含量因子显着抑制了肝细胞癌的生长。