Inositol Hexaphosphate Regulates Colorectal Cancer Cell Cycle And Proliferation Via The Akt/GSK-3?/?-catenin Signaling Cascade In A 1,2-dimethylhydrazine Induced Rat Model

Objective: To investigate the mechanism of phytic acid in regulating cell cycle of colorectal cancer via Akt/GSK-3?/?-catenin signaling pathway.Methods: Sixty Wistar rats were randomly assigned to control group,model group,low-dosage phytic acid group,medium-dosage phytic acid group and high-dosage phytic acid group.Control group and model group were given 0.5%(w/v)saline daily by gavage,meanwhile three phytic acid groups were given sodium phytate daily at the dosage of 0.25g/kg,0.5g/kg,1.0/kg body weight respectively.18 weeks of DMH injection was given to model group,low-dosage phytic acid group,medium-dosage phytic acid group and high-dosage phytic acid group after four weeks of phytic acid administration.Body weights of the rats in the five groups were recorded every two weeks.After rats were sacrificed,tumor incidences of the five groups were analyzed.We examined the expression of genes encoding proteins involved in the PI3K/Akt and Wnt pathways,at the transcriptional and translational levels in a DMH-induced rat colorectal cancer model under different concentrations of phytic acid administration.The cell cycle analysis was determined by flow cytometry.And the cell proliferation was observed by immunohistochemical staining.Results: Compared with the model group,rats in phytic acid treated groups had a smaller body weight loss.And phytic acid could inhibit tumors,in terms of tumor incidence,number,weight and volume,in DMH-induced rats.Additionally,Akt and c-Myc m RNA levels significantly decreased following phytic acid intervention(P<0.05),while no significant change was observed in GSK-3? and ?-catenin m RNA expression(P>0.05).Phytic acid was also shown to downregulate Akt,p Akt,p GSK-3?,c-Myc protein expression and upregulatep?-catenin protein expression(P<0.05).Tumor tissues from DMH-induced rats treated with phytic acid showed G1 phrase arrest,S phrase(P<0.05)and proliferation suppression(P<0.05).Conclusion: In conclusion,phytic acid may have the ability to suppress the proliferation in CRC.And this process may be related to crosstalk between the PI3K/Akt and Wnt pathways,revealing a potential mechanism of CRC chemoprevention by phytic acid in our model.