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

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BMC Cancer

, 10:379

First Online: 20 July 2010Received: 12 April 2010Accepted: 20 July 2010DOI: 10.1186-1471-2407-10-379

Cite this article as: Rückert, F., Samm, N., Lehner, AK. et al. BMC Cancer 2010 10: 379. doi:10.1186-1471-2407-10-379


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.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-10-379 contains supplementary material, which is available to authorized users.

Robert Grützmann and Christian Pilarsky contributed equally to this work.

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Autor: Felix Rückert - Nicole Samm - Anne-Kathrin Lehner - Hans-Detlev Saeger - Robert Grützmann - Christian Pilarsky


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