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

BMC Cancer
Felix RückertChristian Pilarsky

Abstract

Pancreatic 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. From 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. Simultaneous 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 c...Continue Reading

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Citations

Jan 30, 2013·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·P LiuZ Tu
Aug 17, 2012·BMC Cancer·Anke Van den BroeckHugo Vankelecom
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Mar 21, 2016·Nanomedicine : Nanotechnology, Biology, and Medicine·Zhongqiu WangDonghui Li
May 31, 2014·The International Journal of Biochemistry & Cell Biology·Lin Li, Po Sing Leung
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Jan 1, 2010·Cancers·Nicole SammChristian Pilarsky
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Methods Mentioned

BETA
flow cytometry
transfection
FCS
PCR
caspase assay
transfections
FACS

Software Mentioned

AIDA
SPSS
Raytest

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