Discussion
IP6+INS was more effective in inhibiting liver metastasis of colorectal cancer than IP6 or INS alone. The better inhibition effect may be accomplished through regulating the mutation of Wnt/β-catenin signaling pathway by inhibiting Wnt10b, Tcf7, β-catenin, and c-Myc from abnormally high expression.
Methods
The inhibitory effects of IP6, INS and the combination of IP6+INS on tumor progression and liver metastasis of colorectal cancer were investigated in an orthotopic transplantation model of colorectal cancer. The tumor-bearing mice were selected by in vivo bioluminescence imaging and were treated with IP6, INS, and IP6 combined with INS, respectively. All mice were sacrificed after 6 weeks of treatment. The cancer development and metastasis were compared among the groups. The expression of genes related to the Wnt/β-catenin in the model was analyzed.
Results
The results demonstrated that liver metastasis was inhibited after treatment with IP6, INS, and IP6+INS. Compared to that of the M_G, survival period was extended, and tumor weight was lowered in IP6_G, INS_G, and IP6+INS_G. Besides, the liver metastatic area of mice in IP6+INS_G was relatively smaller than that in M_G, IP6_G, or INS_G. The results of RNA-seq analysis showed that the expressions of Wnt10b, Tcf7, and c-Myc were significantly downregulated in IP6+INS_G compared to that in M_G (P<0.05). Results of real-time PCR and Western blot showed that mRNA and protein expressions of β-catenin, Wnt10b, Tcf7, and c-Myc were significantly lower in IP6+INS_G compared to that in M_G (P<0.05).