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Targeting sphingosine kinase 1 with LNA oligonucleotides in gastric cancer

Authors
Journal
BMC Pharmacology
1471-2210
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Volume
8
Identifiers
DOI: 10.1186/1471-2210-8-s1-a51
Keywords
  • Meeting Abstract
Disciplines
  • Biology
  • Medicine

Abstract

1471-2210-8-S1-A51.fm BioMed Central Page 1 of 1 (page number not for citation purposes) BMC Pharmacology Open AccessMeeting abstract Targeting sphingosine kinase 1 with LNA oligonucleotides in gastric cancer Thorsten Füreder1, Doris Hoeflmayer1, Bo Hansen2 and Volker Wacheck*1 Address: 1Department of Clinical Pharmacology, Medical University Vienna, 1090 Vienna, Austria and 2Santaris Pharma A/S, 2970 Hørsholm, Denmark Email: Volker Wacheck* - [email protected] * Corresponding author Background Gastric cancer is the fourth most common cancer world- wide. Despite advances in diagnosis of gastric cancer, the prognosis at advanced stage of disease with the current chemotherapeutic treatment strategies remains poor. Hence, new agents and molecular targets for gastric cancer therapy are desperately needed. Sphingosine kinase 1 rep- resents a promising novel target for anti-cancer therapy. However, the most common used small molecule inhibi- tors of SphK are unspecific inhibitors of SphK1. Here we investigated the effect of targeted downregulation of SphK1 by locked nucleic acid antisense oligonucleotides (LNA-ASO) in gastric cancer cell lines. Materials and methods MKN28 and NCI-N87 gastric cancer cell lines were assessed for cell proliferation and cell death electronic cell counting and FACS analysis, respectively. Target modula- tion of Sphk1 mRNA was assessed by real-time reverse transcriptase PCR. For combination therapy, Sphk1 LNA- ASO was combined with doxorubicin and analyzed for cell growth and apoptosis. Results LNA-ASO targeting SphK1 reduced SphK1 mRNA levels in a dose dependent manner (1.9–4.9-fold) whereas the control LNA-ASO did not lower Sphk1 mRNA levels at all. We next assessed the biological relevance of SphK1 down- regulation by LNA with respect to anti-proliferative activ- ity. Following transfection with 12.5 nM Sphk1 LNA-ASO we observed growth inhibition of MKN28 gastric cancer cells (up to 57%) beginning from 24 h after transfection.

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