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

体外实验表明，抗癌药物AS2-1通过抑制人结肠癌细胞株(KM12SM、SW620、SW1417、Colo206、HCTI16)的G1期细胞增殖和诱导细胞凋亡，呈剂量和时间依赖性抑制细胞增殖。AS2-1上调KM12SM和HCT116细胞周期蛋白D和E的蛋白表达，下调p-16和p21的蛋白表达，从而下调磷酸化Rb的蛋白水平。5 mg/mlAS2-1通过下调XIAP，上调caspase3和caspase8的表达，诱导肿瘤细胞凋亡。甲基扫描DNA芯片研究表明，AS2-1可使多种基因的高甲基化正常化或降低。应用裸鼠结肠癌原位移植瘤切除模型，AS2-1能显著减少肺转移，延长生存时间。(临床研究)我们进行了一项肝切除术后结直肠癌肝转移的随机对照研究。1998年至2004年对患者行肝动脉化疗联合或不联合5-FU化疗。两组无瘤生存率差异无统计学意义，但抗癌栓组的生存率有高于对照组的趋势。抗肿瘤药物的有效性还需要进一步的追踪研究。抗肿瘤药物在结直肠癌中是有效的，特别是在辅助性环境下与细胞毒性化疗药物联合使用时。

(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.