〔Abstract〕 Objective To explore the mechanism by which the inhibitor WZB117 affects the stemness and glycolysis via the downregulation of Yes-related proteins in patient-derived gastric cancer cells. Methods Patient-derived gastric cancer cells were obtained via the trypsin digestion of clinical gastric cancer tissues and incubation. The cells were divided into normal group,low glucose control group and WZB117 treatment group. Afterwards,qRTPCR was used to detect the expression levels of stemness-related genes( Nanog,oct-4 and sox-2),invasion-related genes matrix metalloproteinase-2( MMP-2) and matrix metalloproteinase-9( MMP-9),and apoptosis-related genes( Bcl-2,bax and Cyt-C). Western blot was applied to determine the expression levels of YAP,metabolism-related proteins hexokinase 2( HK2) and pyruvate kinase M2 subtype( PKM2) and activated cysteine-containing aspartate proteolytic enzyme 3( Cleaved Caspase-3). Thiazolyl blue( MTT),plate clone,scratch test,Transwell and kit were performed to measure the cell proliferation,clone formation,migration,invasion,and content of adenosine triphosphate( ATP) and lactic acid,respectively. Results After WZB117 cultured cells,the YAP expression level was significantly lower than that of the normal group and the low glucose control group( P<0. 05),and that of stemness-related genes( Nanog,oct-4 and sox-2) and cell proliferation,clone formation,invasion,and migration were also lower( P<0. 05). The levels of Cleaved Caspase-3 and apoptosis in group treated by WZB117 were higher than those in control groups( P<0. 05),and the expression level of Bcl-2 decreased with the increase of WZB117 concentration( P<0. 05),and the expression levels of Bax and CYT-C increased with the increase of WZB117 concentration( P<0. 05). The content of ATP and lactic acid in supernatant and the protein expression levels of HK2 and PKM2 were lower than those in control groups. Conclusion WZB117 can down regulate the expression of Yap,HK2 and PKM2 in gastric cancer cells,inhibit glycolysis and reduce ATP level.