Myo-inositol Inhibits The Development And Progression Of Pancreatic Cancer By EMT

Objective: The incidence and mortality of pancreatic cancer have gradually increased recent years,which is characterized by high malignancy and poor prognosis.The main reason for poor prognosis of pancreatic cancer patients is that the tumor is highly malignant,prone to peripancreatic invasion and distant metastasis,and insensitive to radiotherapy and chemotherapy.However,the understanding of the molecular mechanism and effective treatment of pancreatic cancer is not yet mature.Therefore,new methods to improve the prognosis of pancreatic cancer patients are necessary.In addition,EMT is closely related to the occurrence and development of pancreatic cancer.The objective of this experiment was to investigate the effect of myo-inositol treatment on pancreatic cancer and the related molecular changes of EMT after myo-inositol treatment.Methods: First,myo-inositol powder was used to prepare a 40mg/ml solution to treat pancreatic cancer cells,MTT method to verify whether it played a role in the proliferation of pancreatic cancer cells.Myo-inositol and gemcitabine was added together to affect pancreatic cancer cells,and observe whether myo-inositol can reduce the resistance of pancreatic cancer cells to gemcitabine.Then the cells were treated with myo-inositol solution,and the inhibition of inositol on the invasion and migration of pancreatic cancer cells was observed by using the transwell method.Next,ISYNA1 was knocked out and treated myo-inositol at the same time to study the changes of proliferation,invasion and migration of pancreatic cancer cells.Cell proteins were extracted,and WB verified that the changes of E-cad,ZEB-1,ISYNA1 after myo-inositol treatment and confirmed the mechanism of myo-inositol acting on pancreatic cancer cells.At last,panc02 cells were injected into the spleen of mice to establish a liver metastasis model.The control group and experimental group mice were fed with normal diet and myo-inositol diet respectively.One month later,the tumorigenesis of mice liver and the changes of tumor tissue WB and immunohistochemistry were observed.Result: MTT suggests that myo-inositol treatment has a significant inhibitory effect on Panc-1,Capan-2 and Miapaca-2,and transwell suggests that the invasion and migration ability of pancreatic cancer cells is significantly reduced.In addition,ISYNA1 knockout can counteract the inhibition of myo-inositol on the proliferation,invasion and migration of PC cells.Myo-inositol treatment could positively regulate E-cad and ISYNA1,and inhibit the expression of ZEB-1,p AKT,and pm TOR.The WB results of mouse liver tumors showed that the expression of ZEB-1 decreased and the expression of E-cad and ISYNA1 increased in the myo-inositol feed group.Immunohistochemistry of tumor tissue suggested that the expression of E-cad increased,simultaneously the expression of Vimentin has descent in the experimental group.Conclusion: Myo-nositol could inhibit the proliferation,invasion and migration of pancreatic cancer cells,and inhibit the malignant biological behavior of pancreatic cancer.In addition,Myo-nositol inhibited EMT in pancreatic cancer by regulating ISYNA1-ZEB-1 pathway and PI3K-AKT-m TOR pathway.