Simultaneous gene silencing of Bcl-2, XIAP and Survivin re-sensitizes pancreatic cancer cells towards apoptosis

BMC Cancer

Research Article

Felix Rückert¹  Anne-Kathrin Lehner¹  Christian Pilarsky¹  Nicole Samm¹  Robert Grützmann¹  Hans-Detlev Saeger¹ 

[1] Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 47, 01307, Dresden, Germany;

关键词: Pancreatic Cancer;    Pancreatic Cancer Cell;    Pancreatic Carcinoma;    Apoptosis Induction;    Pancreatic Ductal Adenocarcinoma;   

DOI  :  10.1186/1471-2407-10-379

 received in 2010-04-12, accepted in 2010-07-20,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundPancreatic ductal adenocarcinoma shows a distinct apoptosis resistance, which contributes significantly to the aggressive nature of this tumor and constrains the effectiveness of new therapeutic strategies. Apoptosis resistance is determined by the net balance of the cells pro-and anti-apoptotic "control mechanisms". Numerous dysregulated anti-apoptotic genes have been identified in pancreatic cancer and seem to contribute to the high anti-apoptotic buffering capacity. We aimed to compare the benefit of simultaneous gene silencing (SGS) of several candidate genes with conventional gene silencing of single genes.MethodsFrom literature search we identified the anti-apoptotic genes XIAP, Survivin and Bcl-2 as commonly upregulated in pancreatic cancer. We performed SGS and silencing of single candidate genes using siRNA molecules in two pancreatic cancer cell lines. Effectiveness of SGS was assessed by qRT-PCR and western blotting. Apoptosis induction was measured by flow cytometry and caspase activation.ResultsSimultaneous gene silencing reduced expression of the three target genes effectively. Compared to silencing of a single target or control, SGS of these genes resulted in a significant higher induction of apoptosis in pancreatic cancer cells.ConclusionsIn the present study we performed a subliminal silencing of different anti-apoptotic target genes simultaneously. Compared to silencing of single target genes, SGS had a significant higher impact on apoptosis induction in pancreatic cancer cells. Thereby, we give further evidence for the concept of an anti-apoptotic buffering capacity of pancreatic cancer cells.

【 授权许可】

CC BY   
© Rückert et al; licensee BioMed Central Ltd. 2010