Effects Of Inositol Hexaphosphate On EMT And MMPs In Tumor Metastasis Of Colorectal Cancer In Rats

Objective:The dimethylhydrazine(DMH)chemical method was conducted to establish istar rats induced colorectal cancer and metastasis model,and the model ould be used to research the effect of different concentration of Inositol exaphosphate(IP6)on colorectal cancer development and metastasis nhibition.The molecular biology related indexes would be further detected to explore the effect of IP6 on the Matrix metalloproteinases,the invasion and metastasis of cancer and the regulation of cell adhesion.Method: Sixty Wistar rats was divided into 5 groups with 12 rats for each according to weight by random block design.These groups were defined as control group (CG),model group(DG),IP6 low-dose group(LG),IP6 middle-dose group (MG)and IP6 high-dose group(HG).The IP6-related groups were given by gavage once a day of sodium phytate with 0.25g/kg,0.5g/kg and 1.0 g/kg,respectively.Meanwhile,the control group and model group were given a gavage with the same dose of normal saline.One month later,the whole groups except the control one would be given an injection of 30mg/kg of DMH to induce colorectal cancer for once a week with 18 weeks.Then,all of the rats continued feeding for 16 weeks until the end of the experiment.The expression of E-cadherin,TGF-?,VEGF,matrix metalloproteinase and MMPs(MMP-2?MMP-9?TIMP-1?TIMP-2)m RNA would be detected by real-time PCR method.The protein expression levels of E-cadherin?TGF-??VEGF?MMP-9 were detected by Western-blotmethod.Results:The control group,model group and IP6 low,medium and high dose groupwere 0%,100%,100%,88.9%,and the lymph node metastasis rate was: 0%,62.5%,40%,25%,16.67%.3 cases of liver metastases were found in modelgroup,2 cases,1 cases with low dose of IP6;expression of E-cadherin proteinand m RNA IP6 dose increased,compared with the other groups there werestatistically significant differences(P < 0.05);decreased with the increasedexpression of IP6 m RNA and VEGF TGF-beta dose(P < 0.05).Comparedwith the model group,the high expression of TGF-IP6 were decreased in low(P < 0.05),in the high dose group decreased expression of VEGF(P < 0.05),TGF-beta,VEGF protein with the results of m RNA were similar in high IP6low expression of VEGF were decreased compared with model group(P<0.05 with the increase of the dose of IP6);MMP-2,MMP-9,TIMP-1,TIMP-2 m RNA expression decreased(P < 0.05),compared with the modelgroup,the high expression of TIMP-1 were decreased in low IP6(P < 0.05),IP6 in high dose group MMP-2,MMP-9 and TIMP-2 expression havedecreased(P < 0.05);MMP The results of-9 protein were similar to those of m RNA.The expression of MMP-9 in the low and high IP6 group was lowerthan that in the model group(P < 0.05).Conclusion: IP6 could inhibit the development of DMH induced colorectal cancer,andit could also reduce the rate of lymph node metastasis.Meanwhile,theinhibitory effect would be more signficant with the IP6 dosage increased.Theinhibitory effect of neoplasm metastasis for IP6 could be related to theregulatingepithelial mesenchymal conversion function of tumor cells.What'smore,IP6 could also increase the adhesion of tumor cells,reduce degradationof extracellular matrix by matrix metalloproteinases,and Inhibit theformation of blood vessels and lymphatic vessels to inhibit tumor metastasis.