Dual Effects Of The BET Inhibitors OTX015 On The Gastric Cancer

BET inhibitors are small molecular inhibitors that target bromodomain-containing proteins.Currently,BET inhibitors are being tested as a class of anti-cancer drugs in clinical trials.In this study,we found that OTX015,a novel BET inhibitor,could not only inhibit the proliferation of gastric cancer cells,but also promoted their apoptosis.In addition,we discovered that OTX015 could inhibit the expression of PD-L1 in gastric cancer cells.In further research,we found that OTX015 targets the proteins BRD2 and BRD4,which can bind to the promoter region of PD-L1,thus promoting the expression of PD-L1.By using OTX015,BRD2 and BRD4 proteins cannot bind to the promoter region of PD-L1,thus inhibiting the transcriptional activity of PD-L1.Furthermore,when PBMCs were used in combination with OTX015,we found that cytotoxicity was significantly enhanced.This suggests that OTX015 can promote the ability of the immune system to fight off cancer cell growth.Finally,we found a significant correlation between the expression of PD-L1 and BRD2/BRD4 in patient samples.We also discovered that the expression levels of PD-L1 were significantly correlated with the patients’ survival.This suggests that OTX015 may be a potential dual-acting anti-cancer drug that can not only kill tumor cells through pharmacological action,but also endogenously reduce the expression of PD-L1,thus promoting autoimmune function.