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

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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