Caudatin Affects Cell Proliferation In Gastric Cancer Cells Through Modulation Of Wnt/β-catenin Signaling

A lot of papers have indicated that caudatin could inhibit cells proliferation and induce cells apoptosis,such as gastic carcinoma, hepatic carcinoma and lung cancer,which was considered that caudatin possesses the characteristics of anti-tumor.Although it has reported that caudatin could inhibit gastric cells proliferation and induce cells apoptosis,few studies have revealed the underlying mechanisms of caudatin in gastic cells.In our present study, we detected the influence of caudatin on gastric cells (AGS and HGC-27) in proliferation by using MTT assay, we also analyed the effect of caudatin on gastric cells (AGS and HGC-27) in apoptosis through the methods of Hoechst33258staining and FACS assays.In addition, Western blot analysis demonstrated that Caspase-9, Caspase-3, Caspase-8and PARP were activated,which resulted in cell apoptosis. FACS assays showed that caudatin induced G1/S arrest and down-regulated the expression of CDK2,yet, the protein of the p21levels was up-regulated in a dose-dependent manner. These results indicated that caudatin could inhibit gastric cells proliferation,inducing apoptosis in a dose-and time-dependent way.Western blot analysis and Immunofluorescence staining indicated that caudatin induced a decrease in the expression of P-catenin and this reduction was on account of proteosome-mediated degradation. This kind of reduction in β-catenin was the result of the down-regulation of its downstream targets genes (cyclinD1and c-MYC) in those two kind of gastric carcinoma cell lines. Furthermore,the expression of miR-372was anomalous in AGS cells and gastric adenocarcinoma tissues,comparing with the normal cells tissuses. We found that the expression of oncomir miR-372and miR-21gradually decreased, while the expression of tumor suppressor let-7a miRNA was up-regulated accompanying by the higher and higher caudatin.Our results show that caudatin inhibits the proliferation of and triggers the apoptosis of gastric cells (AGS and HGC-27) by modulating Wnt/β-catenin cell signaling pathway.This reveals a new mechanism of anti-tumor of caudatin and provides a novel method to the clinic treatment of gastric adenocarcinoma.