TGF-β receptor inhibitor LY2109761 enhances the radiosensitivity of gastric cancer by inactivating the TGF-β/SMAD4 signaling pathway.

ABSTRACT: Radiotherapy is used to treat gastric cancer (GC); however, radioresistance challenges the clinical outcomes of GC, and the mechanisms of radioresistance in GC remain poorly understood. Here, we report that the TGF-β receptor inhibitor, LY2109761 (LY), is a potential radiosensitizer both in vitro and in vivo. As per the Cancer Genome Atlas database, TGF-β overexpression is significantly related to poor overall survival in GC patients. We demonstrated that the TGF-β/SMAD4 signaling pathway was activated in both radioresistant GC cells and radioresistant GC patients. As a TGF-β receptor inhibitor, LY can enhance the activities of irradiation by inhibiting cell proliferation, decreasing clonogenicity and increasing apoptosis. Moreover, LY attenuated the radiation-induced migration and invasio

SUBMITTER: Yang T 

PROVIDER: S-EPMC6834415 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature