Autotaxin delays apoptosis induced by carboplatin in ovarian cancer cells

Cell Signal. 2010 Jun;22(6):926-35. doi: 10.1016/j.cellsig.2010.01.017. Epub 2010 Jan 25.


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 When serum was withdrawn to remove exogenous LPA, ccPA caused a pronounced potentiation of apoptosis induced by carboplatin in cells expressing autotaxin.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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis*
  • Carboplatin / pharmacology*
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Humans
  • Multienzyme Complexes / antagonists & inhibitors
  • Multienzyme Complexes / genetics
  • Multienzyme Complexes / physiology*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Phosphodiesterase I / antagonists & inhibitors
  • Phosphodiesterase I / genetics
  • Phosphodiesterase I / physiology*
  • Phosphoric Diester Hydrolases
  • Pyrophosphatases / antagonists & inhibitors
  • Pyrophosphatases / genetics
  • Pyrophosphatases / physiology*
  • RNA Interference


  • Antineoplastic Agents
  • Multienzyme Complexes
  • Carboplatin
  • Phosphoric Diester Hydrolases
  • Phosphodiesterase I
  • alkylglycerophosphoethanolamine phosphodiesterase
  • Pyrophosphatases