Investigation of the inhibitory mechanism at the hepatic metastasis of the colorectal carcinoma by synthesic retinoid, TAC-101

在结直肠癌中，转移是对死亡率产生不利影响的关键问题。约40%的晚期结直肠癌患者发生肝转移。如果能减少肝转移，晚期大肠癌患者的预后将得到改善。癌症转移是通过复杂的多步骤过程完成的。我们建立了一套大鼠肝转移的磁共振成像（MRI）评估系统，以研究这一复杂的转移过程。我们还建立了内皮细胞侵袭实验方法。近年来，视黄酸（RA）是最有希望的抗肿瘤药物之一，其抗肿瘤作用具有多种机制。在动物模型系统中，RA已经显示出抑制各种上皮组织中的癌发生。RA对肿瘤的作用机制可能与其对肿瘤细胞增殖和分化的影响有关。TAC-101是一种新的人工合成的抗真菌剂 ...更多信息 1份报告表明TAC-101在裸鼠体内实验和体外实验中具有抗肿瘤活性和抗转移活性。(1)每日口服TAC-101可显著抑制肝转移。(2)与对照组相比，TAC-101治疗组大鼠肝转移瘤的MVD显著降低。(3)与对照大鼠相比，用TAC-101处理的肝转移性肿瘤的血管内皮生长因子（VEGF）表达降低。(4)与对照组相比，TAC-101处理组大鼠肝转移瘤的凋亡指数显著增加。(5)TAC-101治疗组大鼠肝转移瘤的Fas表达较对照组显著增加。这些数据表明，TAC-101对肝转移的抑制作用是通过抑制VEGF表达抑制血管生成的抑制作用以及通过FAS诱导细胞凋亡。少

In colorectal cancer, metastasis is a critical problem which adversely affects mortality rates. About 40% of patients with advanced colorectal cancer developed hepatic metastasis. If the hepatic metastasis will be reduced, the prognosis of the patients with advanced colorectal cancer will be improved. Cancer metastasis is completed through complex and multistep processes. We developed an evaluate system of hepatic metastasis in rats by magnetic resonance imaging (MRI) in time course to investigate this complex metstatic processes. We also developed the invasion assay method using endothelial cell. Recently, retinoic acid (RA) is one of the most expected anti-cancer agents, and has several mechanism on cancer therapy. RA have been shown to supress carcinogenesis in various epithelial tissues in animal model systems. The mechanism of action of RAs on tumors seems to be related to their effects on proliferation and differentiation of the tumor cells. TAC-101 is a novel synthesic RA.Severa … More l reports indicated the anti-tumor activity and anti-metastatic activity of TAC-101 on the experiments using nude mice in vivo and the experiments in vitro. (1) Daily oral administration of TAC-101 resulted in a significant inhibition of hepatic metastasis. (2) MVD of the hepatic metastatic tumor in the rats treated with TAC-101 was significantly decreased as compared with that of control rats. (3) vascural endothelial growth factor (VEGF) expression of the hepatic metastatic tumor treated with TAC-101 was reduced as compared with that of control rats. (4) The apoptotic index of the hepatic metastatic tumors in the rats treated with TAC-101 was significantly increased as compared with that of the control rats. (5) Fas expression of the hepatic metastatic tumor in the rats treated with TAC-101 was remarkably increased as compared with that of control rats. These data indicate that the inhibitory effect of the hepatic metastasis by TAC-101 is the inhibitory effect of angiogenesis via the supression of VEGF expression and also induction of apoptosis via FAS. Less