Simultaneous gene silencing of KRAS and anti-apoptotic genes as a multitarget therapy
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
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.
Details
Original language | English |
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Pages (from-to) | 3984-3992 |
Number of pages | 9 |
Journal | Oncotarget |
Volume | 7 |
Issue number | 4 |
Publication status | Published - 26 Jan 2016 |
Peer-reviewed | Yes |
External IDs
researchoutputwizard | legacy.publication#73687 |
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researchoutputwizard | legacy.publication#73286 |
Scopus | 84957990562 |
PubMed | 26716649 |
PubMedCentral | PMC4826184 |
Keywords
Sustainable Development Goals
Keywords
- Adaptor Proteins, Signal Transducing/genetics, Animals, Apoptosis, Blotting, Western, Cell Proliferation, Female, Gene Silencing, Humans, Inhibitor of Apoptosis Proteins/genetics, Mice, Myeloid Cell Leukemia Sequence 1 Protein/genetics, Pancreatic Neoplasms/genetics, Proto-Oncogene Proteins p21(ras)/antagonists & inhibitors, RNA, Messenger/genetics, RNA, Small Interfering/genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Survivin, Tumor Cells, Cultured, X-Linked Inhibitor of Apoptosis Protein/genetics, Xenograft Model Antitumor Assays, bcl-X Protein/genetics