Geburtshilfe Frauenheilkd 2008; 68 - PO_Onko_01_47
DOI: 10.1055/s-0028-1088845

The effect of the Aurora-kinase inhibitor AZD1152-HQPA on primary ovarian cancer cell culture specimens

C Schem 1, CB Maas 2, K Bräutigam 2, DO Bauerschlag 3, N Arnold 2, J Weimer 2
  • 1Universitätsfrauenklinik Kiel, UK-SH, Campus Kiel, Kiel
  • 2Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik Gynäkologie u. Geburtshilfe, Kiel
  • 3Klinik für Gynäkologie und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel

Objective:

Aurora kinases (Aurk) are involved in organizing the mitotic spindle apparatus, monitoring the correct chromosome segregation and are required for the process of cytokinesis. In many cancer entities including breast and ovarian cancer, AurkA and AurkB are overexpressed. AZD1152-HQPA is an aurora kinase inhibitor with enhanced selectivity for aurora B, causing a failure of chromosome segregation, followed by DNA endoreduplication and cell death. The post-operative treatment of ovarian cancer usually includes the application of the mitotic inhibitors Paclitaxel or Docetaxel that cause mitotic arrest.

Methods:

We have analysed the effect of AZD1152-HQPA on 48 primary ovarian cancer cell lines established from tumor ascites or tumor specimens. The cell lines are known to show different level of taxane resistance. We characterized the effects of combined treatment of cells with Paclitaxel or Docetaxel and AZD1152-HQPA with that of the respective monotherapy by MTT-assays.

Results:

In our cell cultures AZD1152 had a growth suppressing effect in 30 of 48 primary cell cultures when used as a single agent. In combination with taxane the suppressing effect was antagonised by 10 nM AZD1152 in 27 of those 30 tests. Cells treated with a low and non-suppressing paclitaxel concentration were suppressed by 10 nM AZD1152. Cells treated with a suppressing paclitaxel concentration were loosing this inhibition in combination with 10 nM AZD1152.

Conclusions:

Interestingly various levels of taxane resistance provoke different aurora kinase inhibitor effects. Further work is required to analyse the dependency of treatment and the interaction of taxanes and AZD1152 in these cell lines.

Aurora-kinase - ovarian cancer - taxan