Lee Soo Jin, Ohashi Yasukata, Sakurai Hiroaki, Saiki Ikuo
Department of Pathogenic Biochemistry, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Cancer Lett. 2003 Aug 20;198(2):169-77. doi: 10.1016/s0304-3835(03)00306-9.
The anti-metastatic effect of 4-[3,5-bis(trimethylsilyl)benzamido]benzoic acid (TAC-101) was investigated using our established intrahepatic metastasis model. Orthotopic implantation of a fragment of CBO140C12 hepatoma into the liver resulted in the formation of a solitary tumor nodule and its intrahepatic metastasis. Daily oral administration of TAC-101 at a dose of 8 mg/kg resulted in a significant inhibition of intrahepatic metastasis, but did not affect the growth of the tumor at the implanted site. The down-regulation of transcriptional anti-activator protein-1 (AP-1) activity by TAC-101 paralleled the inhibition of cell invasion and migration through the repression of expression of the mRNAs for urokinase-type plasminogen activator (u-PA) and its receptor (u-PAR). These findings suggest that TAC-101 may improve therapeutic efficacy for liver cancer patients to prevent intrahepatic metastasis.
使用我们建立的肝内转移模型研究了4-[3,5-双(三甲基甲硅烷基)苯甲酰胺基]苯甲酸(TAC-101)的抗转移作用。将CBO140C12肝癌组织片段原位植入肝脏，导致形成单个肿瘤结节及其肝内转移。每日口服剂量为8 mg/kg的TAC-101可显著抑制肝内转移，但不影响植入部位肿瘤的生长。TAC-101对转录反式激活蛋白-1(AP-1)活性的下调与通过抑制尿激酶型纤溶酶原激活剂(u-PA)及其受体(u-PAR)的mRNA表达来抑制细胞侵袭和迁移平行。这些发现表明，TAC-101可能提高肝癌患者预防肝内转移的治疗效果。
