Dual induction of apoptotic and autophagic cell death by targeting survivin in XXXX .

@entity1 @entity5 @entity996 @entity19 @entity67443 @entity3607 @entity8783 @entity21684 @entity1205 @entity213
Survivin is ubiquitously expressed in @entity1 with @entity213 ( @entity213 ) and is associated with poor survival and chemotherapy resistance. @entity67443 ( @entity67443 ) is a selective survivin suppressant that exhibits potent antitumor activities by inducing apoptosis and autophagy in various types of @entity5 . However, the curative effects and underlying mechanisms of @entity67443 in @entity213 remain unclear. This study showed that survivin overexpression positively correlated with p-S6, @entity996 and @entity3607 but negatively correlated with the autophagic marker @entity21684 in @entity1 @entity213 tissues. In vitro studies revealed that @entity67443 triggered apoptosis of @entity213 cells in mitochondria and death receptor-dependent manner. The treatment also significantly enhanced autophagy by upregulating @entity8783 , which led to cell death. @entity67443 not only downregulated the expression of survivin but also remarkably suppressed the activation of the mTOR signaling pathway in vitro and in vivo. @entity67443 displayed potent antitumor activities in both CAL27 xenograft and transgenic @entity213 @entity19 models by delaying @entity5 onset and suppressing @entity5 growth. Furthermore, @entity67443 combined with @entity1205 promoted @entity5 regression better than either treatment alone without causing considerable body weight loss in the @entity213 xenograft models. Overall, targeting survivin by @entity67443 can benefit @entity213 therapy by increasing apoptotic and autophagic cell death, and suppressing prosurvival pathways.
