GenomeRNAi - a database for RNAi phenotypes and reagents
TitleScreen TitleAssayBiomodelSpecies
Autotaxin delays apoptosis induced by carboplatin in ovarian cancer cells. Vidot et al. (2010) Combinatorial effect with paclitaxel (3) Viability (synthetic lethal)OVCAR-3H. sapiens

Abstract

Drug resistance remains a barrier to the effective long term treatment of ovarian cancer. We have established an RNAi-based screen to identify genes which confer resistance to carboplatin or paclitaxel. To validate the screen we showed that siRNA interfering with the apoptosis regulators FLIP and Bcl-X(L) conferred sensitivity to paclitaxel and carboplatin respectively. The expression of 90 genes which have previously been shown to be over-expressed in drug-resistant ovarian cancer was inhibited using siRNA and the impact on sensitivity to carboplatin and paclitaxel was assessed. ENPP2 was identified as a candidate gene causing drug resistance. ENPP2 encodes autotaxin, a phospholipase involved in the synthesis of the survival factor lysophosphatidic acid. siRNA directed to ENPP2 resulted in earlier apoptosis following treatment with carboplatin. 2-carbacyclic phosphatidic acid (ccPA 16:1), a small molecule inhibitor of autotaxin, also accelerated apoptosis induced by carboplatin. Stable ectopic expression of autotaxin in OVCAR-3 cells led to a delay in apoptosis. When serum was withdrawn to remove exogenous LPA, ccPA caused a pronounced potentiation of apoptosis induced by carboplatin in cells expressing autotaxin. These results indicate that autotaxin delays apoptosis induced by carboplatin in ovarian cancer cells.

Screen details


Stable Id: GR00207-A-3
Screen title: Combinatorial effect with paclitaxel (3)
Assay: Viability (synthetic lethal)
Method: Colorimetrics
Scope: Selected genes
Screen type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: OVCAR-3
Library: Dharmacon, np
Reagent type: siRNA
Score type: Sensitization index
Cutoff: < 0.75 for both 0.75 and 1.50 IC50
Notes: