The Role Of FXR In Esophageal Cancer Cell

Esophageal cancer is the ninth most common malignant tumor in the world.China is a high incidence area for esophageal cancer where are more than 50%of esophageal cancer patients worldwide.Although the current techniques of diagnosis and treatment for esophageal cancer have made some progress,the survival rate of prognosis is still low.Therefore,it is significant to study the molecular mechanism of esophageal cancer and explore new therapeutic targets.Farnesoid X receptor(FXR)is a member of the nuclear receptor superfamily and plays a key regulatory role in bile acids,lipids and glucose metabolism.At the same time,some studies have shown that FXR is also involved in the development of various cancers.The MAPK signaling pathway is a signaling network composed of a series of catalytic cascades that together regulate a variety of cellular processes including proliferation,differentiation,and migration,and are closely related to cancer progression.In this study,we found that MAPK signaling pathway is antagonized after ligand activation of FXR,thereby inhibiting esophageal cancer.At the cellular phenotype level,RTCA proliferation experiments showed that FXR can inhibit the proliferation of esophageal cancer cells after ligand activation.RTCA migration experiments indicate that activated FXR is able to inhibit cell migration.Double staining experiments showed that activated FXR can promote apoptosis.Single staining experiments showed that activated FXR can promote cell arrestted in G0/G1 phase.At the molecular mechanism level,Western blotting showed that activated FXR can inhibit the phosphorylation of the MAPK signaling pathways p38,ERK1/2 and JNK in esophageal cancer cells.Real-time PCR experiments showed that activated FXR can inhibit the expression of CyclinD1,c-Fos,IL-6,MMP7,TNFa,IL-8,IP-10,MCP-1 mRNA.These results indicate that FXR can antagonize the MAPK signaling pathway by inhibiting the phosphorylation of p38,ERK1/2,and JNK proteins,thereby inhibiting the expression of its downstream genes,other inflammation and cancer-related genes,thereby inhibiting the proliferation and migration,promoting apoptosis and G0/G1 phase arrestting of esophageal cancer cells.In summary,FXR has been shown to have negative regulatory effect on esophageal cancer at the cellular level.This conclusion provides new targets and ideas for the prevention and treatment of esophageal cancer and the development of related specific drugs.