Inhibitory Effects Of Phytate, Inositol And Both On The Liver Metastasis Of Colorectal Cancer In BALB / C Mice

Objective: By using a liver metastasis model of colorectal cancer in BALB/c mice,we examined the inhibitory effect of Inositol hexaphosphate（IP₆） and inositol（Ins） on liver metastasis of colorectal carcinoma, the mechanisms underlying the inhibitory effects of IP₆ and Ins on liver metastasis were explored from the perspective of molecular biology.Methods: Forty-eight tumor bearing mice were injected with CT-26 cells in the spleen were randomly divided into four groups: IP₆ group, Ins group, IP₆+Ins group and normal saline group（n = 12）. Second days after operation, 0.2m L/d was administered via the gastrointestinal tract, the volume of the combination group was 1:1, and the dose of IP₆ and Ins was 80mg/kg. After 20 d all the mice were sacrificed and the tumor inhibiting rates were obtained. The expression of collagen IV, Fibronectin（FN） and Laminin（LN） in liver tissue was assessed by RT-PCR and western-blot analysis. The levels of Integrin-β1 、 Matrix metalloproteinase 9（MMP-9）、Vascular endothelial growth factor（VEGF）、Basic fibroblast growth factor（ b FGF）、Transforming growth factor beta（TGF-β）in liver tissue was assessed by RT-PCR and Immunohistochemistry analysis.Results: Compared with control group, the tumor weight and inhibiting rates of experimental group were significantly reduction（P<0.05）, IP₆+Ins was synergistically superior in growth inhibition than either compound. The m RNA expression of collagen IV, FN or LN was not reduced by treatment with IP₆, Ins, or IP₆+Ins. But the protein expression of collagen IV、FN and LN in the IP₆、Ins group were decreased, the combination group was significantly reduction（P < 0.05）. The protein and m RNA levels of Integrin-β1、MMP-9、VEGF、b FGF、TGF-β were decreased. IP₆+Ins was synergistically superior in growth inhibition than either compound. Experimental group was significantly different from that of control group（P < 0.05）.Conclusion: IP₆, Ins and their combination inhibit the development and metastatic progression of colorectal cancer to the liver in BALB/c mice, and the effect of their combined application was significantly greater than the effect of either compound alone. Its effect on liver metastasis may be related to the adhesion, degradation the ECM and anti-angiogenesis of tumor.