Simultaneous gene silencing of KRAS and anti-apoptotic genes as a multitarget therapy

Werner K, Lademann F, Thepkaysone ML, Jahnke B, Aust DE, Kahlert C, Weitz J, Grützmann R, Pilarsky C, Pilarsky C, Weber G (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Oncotarget Impact Journals

Book Volume: 7

Pages Range: 3984-92

Journal Issue: 4

DOI: 10.18632/oncotarget.6766

Abstract

Pancreatic cancer is one of the most lethal tumor types worldwide and an effective therapy is still elusive. Targeted therapy focused against a specific alteration is by definition unable to attack broad pathway signaling modification. Tumor heterogeneity will render targeted therapies ineffective based on the regrowth of cancer cell sub-clones. Therefore multimodal therapy strategies, targeting signaling pathways simultaneously should improve treatment.SiRNAs against KRAS and the apoptosis associated genes BCLXL, FLIP, MCL1L, SURVIVIN and XIAP were transfected into human and murine pancreatic cancer cell lines. Induction of apoptosis was measured by Caspase 3/7 activation, subG1 FACS analysis and PARP cleavage. The therapeutic approach was tested in a subcutaneous allograft model with a murine cancer cell line.By using siRNAs as a systematic approach to remodel signal transduction in pancreatic cancer the results showed increasing inhibition of proliferation and apoptosis induction in vitro and in vivo. Thus, siRNAs are suitable to model multimodal therapy against signaling pathways in pancreatic cancer. Improvements in in vivo delivery of siRNAs against a multitude of targets might therefore be a potential therapeutic approach.

Authors with CRIS profile

Robert Grützmann Department of Surgery Christian Pilarsky Professur für Chirurgische Forschung Georg Weber Department of Surgery

Involved external institutions

Technische Universität Dresden

Germany (DE)

How to cite

APA:

Werner, K., Lademann, F., Thepkaysone, M.-L., Jahnke, B., Aust, D.E., Kahlert, C.,... Weber, G. (2016). Simultaneous gene silencing of KRAS and anti-apoptotic genes as a multitarget therapy. Oncotarget, 7(4), 3984-92. https://dx.doi.org/10.18632/oncotarget.6766

MLA:

Werner, Kristin, et al. "Simultaneous gene silencing of KRAS and anti-apoptotic genes as a multitarget therapy." Oncotarget 7.4 (2016): 3984-92.

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