Authors: Wolfgang Glienke Eva Hausmann Lothar Bergmann
Publish Date: 2010/12/21
Volume: 32, Issue: 3, Pages: 493-500
Abstract
Signal transducer and activator of transcription 3 STAT3 is a key regulator of cytokine signaling pathways that regulates gene expression In pancreatic cancer constitutive activation of STAT3 contributes to oncogenesis by preventing apoptosis through upregulation of antiapoptotic proteins We have examined the inhibition of STAT3 as a potential therapeutic approach in pancreatic cancer siRNA targeting STAT3 was used to evaluate the role of STAT3 in modulating the expression of Survivin/BIRC5 and BCLxL in the pancreatic cancer cell lines PANC1 and BxPC3 and induction of apoptosis Expression of STAT3 Survivin/BIRC5 and BCLxL on mRNA and protein level was measured by realtime RTPCR and Western blot analysis 24 48 and 72 h after transfection STAT3 downregulation resulted in a decrease of cell viability in both cell lines and induced apoptosis in BxPC3 cells Despite significant inhibition of STAT3 the expression of the antiapoptotic genes Survivin/BIRC5 and BCLxL were not subsequently downregulated Even more the cell line BxPC3 shows a significant increase of Survivin/BIRC5 and BCLxL mRNA after 48–72 h as a result of STAT3 downregulation Inactivation of STAT3 in pancreatic cancer cell lines induces apoptosis but also may promote the expression of antiapoptotic genes
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