@entity7080 inhibitors enhance the effects of cytotoxic agents in XXXX .

@entity43 @entity1 @entity137 @entity5 @entity19 @entity7080 @entity1311 @entity98 @entity1358 @entity4546
UNASSIGNED: This study was designed to investigate whether @entity7080 inhibitors (PPI, V-ATPase blocker) could increase the effect of cytotoxic agents in @entity43 (EOC). Expression of V-ATPase protein was evaluated in @entity1 with EOC using immunohistochemistry, and @entity1 survival was compared based on expression of V-ATPase mRNA from a TCGA data set. In vitro, EOC cell lines were treated with chemotherapeutic agents with or without V-ATPase siRNA or PPI ( @entity4546 ) pretreatment. Cell survival and apoptosis was assessed using @entity98 assay and ELISA, respectively. In vivo experiments were performed to confirm the synergistic effect with @entity4546 and @entity1311 on @entity5 growth in orthotopic and @entity1 -derived xenograft (PDX) @entity19 models. Expression of V-ATPase protein in @entity43 tissues was observed in 44 @entity1 (44/59, 74.6%). Higher expression of V-ATPase mRNA was associated with poorer overall survival in TCGA data. Inhibition of V-ATPase by siRNA or @entity4546 significantly increased @entity137 or apoptosis to @entity1311 in chemoresistant (HeyA8-MDR, SKOV3-TR) and @entity1358 cells (ES-2, RMG-1), but not in chemosensitive cells (HeyA8, SKOV3ip1). Moreover, the combination of @entity4546 and @entity1311 significantly decreased the total @entity5 weight compared with @entity1311 alone in a chemoresistant EOC animal model and a PDX model of @entity1358 . However, this finding was not observed in chemosensitive EOC animal models. These results show that @entity4546 pretreatment can increase the effect of chemotherapeutic agents in chemoresistant EOC and @entity1358 via @entity5 microenvironment.
