Impact And Molecular Mechanism Of Loganin On Epithelial Mesenchymal Transformation Of Gastric Cancer Cells

Background and Objective:Gastric cancer(GC)has become one of prevalent malignant tumors in China in the past 2 decades with 3rd morbidity and 2nd fatality rate due to the poor prognosis.It is well known that invasion and metastasis of gastric cancer tumors is one of the most common causes of death.Studies have shown that epithelial-mesenchymal transition(EMT)is an important initial step in the process of cancer cell invasion and metastasis.Plenty of plants with medication value have been utilized in treating diseases in Chinese Traditional Medication(CTM).Loganin is the main active ingredient in Cornus Officinalis,which has anti-caner and anti inflammation effect,can reduce oxidative stress,also improve memory.These previous researches showed that Loganin had a promised future in cancer treatments,but there is no report regarding how Loganin impact EMT in GC.Therefore,the purpose of this study was to investigate the effect of Loganin on epithelial-mesenchymal transition(EMT)in gastric cancer cells,and to further explore its mechanism at the molecular level.Methods:Human gastric cancer cell lines AGS,BGC823 and SGC7901 were cultured routinely.The effect of Loganin on cells activity was tested by utilizing MTT assay.Also Wound assay and Transwell assay were employed to detect the effect of Loganin on migration and invasion in BGC823 cells.Furthermore,qRT-PCR and Western blot were used to examine the variations of associated genes and PI3K-AKT signal pathway in BGC823 cells prior and post Loganin interventions.Results:Results of MTT assay showed that the activity of BGC823 was lowest among AGS(0.748±0.051),BGC823(0.581±0.042)and SGC7901(0.412±0.037)(F=44.101,P<0.01);the expression level of PCNA mRNA and protein declined gradually with the increase dose of Loganin(F=36.298,47.942,P<0.01).Compared with the control group,the ability of migration and invasion in BGC 823 cells decreased,and this changes were particularly distinct in high dose Loganin group(200mg/L),which were more significant than in low dose group(50mg/L)(migration: F=87.750,P<0.01;invasion: F=85.749,P<0.01).Results of qPCR and Western blot showed that expressions of migration,invasion associated genes in BGC823 cells changes significantly compared with the control group,especially in high dose Loganin group(P<0.01).Results of qPCR and Western blot illustrated that EMT related gene in BGC823 cells changes significantly compared with the control group,especially in high dose Loganin group(P<0.01).The activity of PI3K-AKT signal pathway declined significantly post Loganin intervention,and expression of p-PI3 K,p-AKT decreased significantly,especially in high dose Loganin group(F=38.590,63.563;P<0.01).Conclusion:Loganin inhibits EMT in the human gastric cancer BGC823 cells,and this mechanism may be achieved through the activity of the PI3K-AKT signaling pathway.