Autotaxin delays apoptosis induced by carboplatin in ovarian cancer cells

Susanne Vidot, James Witham, Roshan Agarwal, Sebastian Greenhough, Harnoor S. Bamrah, Gabor Tigyi, Stanley B. Kaye, Alan Richardson

Research output: Contribution to journalArticle

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 When serum was withdrawn to remove exogenous LPA, ccPA caused a pronounced potentiation of apoptosis induced by carboplatin in cells expressing autotaxin.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

Original languageEnglish (US)
Pages (from-to)926-935
Number of pages10
JournalCellular Signalling
Volume22
Issue number6
DOIs
StatePublished - Jun 1 2010

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Carboplatin
Ovarian Neoplasms
Apoptosis
Paclitaxel
Small Interfering RNA
Drug Resistance
Phosphatidic Acids
Phospholipases
RNA Interference
Genes
Gene Expression
Serum
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Vidot, S., Witham, J., Agarwal, R., Greenhough, S., Bamrah, H. S., Tigyi, G., ... Richardson, A. (2010). Autotaxin delays apoptosis induced by carboplatin in ovarian cancer cells. Cellular Signalling, 22(6), 926-935. https://doi.org/10.1016/j.cellsig.2010.01.017

Autotaxin delays apoptosis induced by carboplatin in ovarian cancer cells. / Vidot, Susanne; Witham, James; Agarwal, Roshan; Greenhough, Sebastian; Bamrah, Harnoor S.; Tigyi, Gabor; Kaye, Stanley B.; Richardson, Alan.

In: Cellular Signalling, Vol. 22, No. 6, 01.06.2010, p. 926-935.

Research output: Contribution to journalArticle

Vidot, S, Witham, J, Agarwal, R, Greenhough, S, Bamrah, HS, Tigyi, G, Kaye, SB & Richardson, A 2010, 'Autotaxin delays apoptosis induced by carboplatin in ovarian cancer cells', Cellular Signalling, vol. 22, no. 6, pp. 926-935. https://doi.org/10.1016/j.cellsig.2010.01.017
Vidot, Susanne ; Witham, James ; Agarwal, Roshan ; Greenhough, Sebastian ; Bamrah, Harnoor S. ; Tigyi, Gabor ; Kaye, Stanley B. ; Richardson, Alan. / Autotaxin delays apoptosis induced by carboplatin in ovarian cancer cells. In: Cellular Signalling. 2010 ; Vol. 22, No. 6. pp. 926-935.
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