Endostatin Combined With Radiotherapy Suppresses Invasion Through Inhibition Of Epithelial-mesenchymal Transition In Esophageal Cancer

[Objectives]The growth of solid tumors requires angiogenesis to provide oxy gen and nutrients and to support cell proliferation.The switch from an avascul ar to a vascular phenotype is typically related to acceleration of tumor growth.Antiangiogenic therapy is becoming a very promising way for malignant tumo rs.Meanwhile,malignant tumor cells themselves were able to develop the for mation of cell-lined vessels that contribute to tumor neovascularization and sup ply the nutrients and oxygen,which is called angiogenesis.However,the mole cular mechanism of angiogenesis remains unclear.The purpose of this study w as to investigate the efficacy of the novel recombinant human endostatin(rh-E ndo)protein combined with radiotherapy on human esophageal squamous cell c arcinoma(ESCC)cell lines Eca-109 and TE13,and how rh-Endo influence the ability of Eca-109 and TE13.[Materials and methods]ECA109 and TE13 cells were exposed to a certain dose of radiation treated with rh-Endo(6Gy)at different concentrations.The fl ow cytometry were performed to analyze cell proliferation and apoptosis.The wound-healing migration assay and transwell invasion assay were performed to analyze the migration and invasion of ESCC.The expression of the protein P TEN,Akt,p-Akt,GSK-3?,p-GSK-3,E-cadherin were assessed using Western blot.The results of each experiment are strictly analysis by statistical software.[Results]Results of cck8 assay and flow cytometry showed that rh-Endo do es not improve radiosensitivity of ESCC and the rh-Endo alone does not induc e the apoptosis of ECA109/TE13.The wound-healing migration assay,transwell invasion assay show that the migration and invasion of esophageal cancer cells are inhibited when combined radiation with high concentration of rh-Endo.We stem blot analysis demonstrated that rh-Endo combined with irradiation inhibits migration,invasive of ESCC by inhibiting EMT throught inactivation of AKT/GSK-3? signaling pathway in vitro.[Conclusion]The present study indicated that rh-Endo combined with radiati on significantly change the microenvironment of ESCC and reduce the degree of malignant tumor by regulating the EMT through inactivation of Akt signalin g pathway.