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Anti-tumor effects of biochemical defense modifier antineoplaston again colorectal cancer

生化防御调节剂抗肿瘤素对结直肠癌的抗肿瘤作用

基本信息

批准号：
13671364
负责人：
SHIROUZU Kazuo
金额：
$ 2.56万
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：
2001
资助国家：
日本
起止时间：
2001 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671364/
关键词：
antineoplaston A10, AS2-1 G1 cell arrest apoptosis demethylation colorectal metastasis to the liver post-operative adjuvant chemotherapy randomized clinical trial hepatic arterial infusion chemothera アンチネオプラストン AS2-1 A10-I 大腸癌 G1細胞

项目摘要

(in vitro study)Antineoplaston AS2-1 inhibited colon cancer cell (KM12SM, SW620, SW1417, Colo206, HCTI16) proliferation in a dosage-and time-dependent manner through G1 cell arrest and induction of apoptosis. AS2-1 up-regulated the protein expression of cyclin D and cyclin E, and down-regulated the protein expression of p-16 and p21, resulting down-regulated the protein level of phosphorylated Rb in KM12SM and HCT116 cells. Five mg/ml of AS2-1 induced apoptosis in tumor cells through down-regulation of XIAP and up-regulation of caspase 3 and caspase 8. Methyl scan DNA chip study revealed that AS2-1 normalized or reduced the hyper methylation in various genes.(in vivo study)AS2-1 inhibited the growth and tumorigenecity of implanted colon tumors (KM121SM, HCT116) into the subcutis in nude mice. AS2-1 showed significant reduction in lung metastasis and prolongation of survival time using removal model of orthotopically implanted colon cancer in nude rats.(Clinical study)We have conducted a randomized control study after hepatectomy in colorectal metastasis to the liver. Hepatic arterial infusion chemotherapy using 5-FU with or without antineoplastons was performed in 64 patients between 1998 and 2004. There was no significant difference in disease-free survival rate between the two groups, however the survival rates in antineoplaston group was tended to be higher than that in the control group. Further follow-up should be necessary to conclude usefulness of antineoplastons.Antineoplastons would be effective in colorectal cancer in particular in adjuvant setting in combination with cytotoxic chemotherapeutic agents.

（体外研究）抗肿瘤素AS2-1通过G1细胞阻滞和诱导凋亡，以剂量和时间依赖的方式抑制结肠癌细胞（KM12SM、SW620、SW1417、col206、HCTI16）的增殖。AS2-1上调cyclin D和cyclin E蛋白表达，下调p-16和p21蛋白表达，导致KM12SM和HCT116细胞中磷酸化Rb蛋白水平下调。5 mg/ml AS2-1通过下调XIAP和上调caspase 3、caspase 8诱导肿瘤细胞凋亡。甲基扫描DNA芯片研究表明，AS2-1使多种基因的高甲基化正常化或降低。（体内研究）AS2-1抑制裸鼠皮下植入结肠肿瘤（KM121SM, HCT116）的生长和致瘤性。在裸鼠原位结肠癌切除模型中，AS2-1明显减少肺转移，延长存活时间。（临床研究）我们进行了一项肝切除术后结直肠肝转移的随机对照研究。在1998年至2004年期间，64例患者接受了5-FU肝动脉输注化疗，有或没有抗瘤酮。两组无病生存率无显著性差异，但抗肿瘤激素组生存率有高于对照组的趋势。有必要进一步随访以确定抗瘤酮的有效性。抗肿瘤药物在结直肠癌治疗中是有效的，特别是在辅助治疗中与细胞毒性化疗药物联合使用。