Endostatin Combined With Radiotherapy Inhibit Epithelial-mesenchymal Transition Lead To The Suppression Of Vasculogenic Mimicry Formationin Of Esophageal Cancer

Objective:Radiotherapy is a widely recognized therapeutic in esophageal cancer even at advanced stages.Re-combinant human endostatin(rh-Endo)is a well established anti-angiogenic agent.This study is to investigate the efficacy of the rh-Endo combined with radiotherapy on human esophageal squamous cell carcinoma(ESCC)cell lines Eca-109 and TE13 in the following aspects:proliferation,clone formation,and vaculogenic mimicry(VM),and explore the possible related mechanisms.Methods:EC A109 and TE13 human esophageal squamous cell carcinoma cell lines were treated with rh-Endo at different concentration and radiation.The cell proliferation,clone formation,and radiosensitivity were used to determine the effects of the drug with radiotherapy or not.The 3D culture and tube formation assay were used to estimate whether rh-Endo combined with irradiation would inhibit the esophageal cancer cells metastasis.Western Blotting analysis was ultimately performed to evaluated the efficacy of rh-Endo on the expression of cpithelial-mcsenchymal transition(EMT)and related proteins.Results:Re-combinant human endostatin did not improve the radiosensitivity in vitro,which indicated that the effect of rh-Endo combined with radiotherapy was not lead to direct tumor-cell killing.The cells vaculogenic mimicry formation ability of irradiated esophageal cancer has been increased in irradiated groups compared with non-irradiated.rh-Endo significantly inhibited the vaculogenic mimicry formation ability of ESCC cells ECA109 and TE13 in both non-irradiated groups and irradiated groups with a dose-dependent relationship mpressively.The results obtained from Western Blotting analysis showed that E-cadherin and ?-catenin was decreased after irradiation,which leading to the increase of Snail and N-cadherin remarkably in both ECA109 and TE13.All of these trends reversed when adding rh-Endo into each treatment group,that rh-Endo combined with irradiation inhibits EMT through inactivation of Snail/E-cadherin signaling pathway in ESCC.Conclusions:Radiotherapy of esophageal cancer inhibited the proliferation and clone formation of tumor cells,but increased tumor cells' vaculogenic mimicry ability.rh-Endo could nether directly inhibit the proliferation nor reduce clone formation of esophageal cancer cells.Whereas,it suppressed tumor cells' vasculogenic mimicry formation ability after irradiation through inhibition of epithelial-mesenchymal transition in esophageal cancer.