Published in:
01-10-2009 | Original Article
The relative activity of cisplatin, oxaliplatin and satraplatin in testicular germ cell tumour sensitive and resistant cell lines
Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2009
Login to get accessAbstract
Background
Germ cell tumours (GCT) can become resistant to cisplatin, which is associated with a relatively poor prognosis. Oxaliplatin and satraplatin have been developed to overcome cisplatin resistance in other cancers, but their effect in cisplatin resistant (cisR) GCTs is unclear. In this work we address this issue by comparing their efficacy in three paired sensitive and cisR GCT cell lines.
Methods
Three established cisplatin sensitive (cisS) and resistant cell line pairs were used (GCT27, GCT27r: SUSA, SUSAr: 833k, 833kr). Viability was assessed using a luciferase based ATP assay and EC50 and EC80 concentrations were calculated. Western blot analysis and flow cytometry was used for further assessment.
Results
Sensitivity to the three platinum compounds was broadly similar in the three cisS lines GCT cell lines (EC50 = 0.27–0.51 μM for cisplatin, 0.52–0.79 μM for oxaliplatin, 0.31–1.26 μM for satraplatin). EC50 values for cisplatin in the three cisR sub lines were 1.8- to 3.8-fold higher than in the sensitive parental lines. Cross resistance to satraplatin and oxaliplatin occurred in all three cisR cell lines (resistance factor 1.9–4.4), with the exception of oxaliplatin in the 833Kr (resistance factor 0.9). Differences in the effect of specific drugs on cell cycle distribution, p53, p21 and MDM2 were observed.
Conclusions
These data suggest that satraplatin and oxaliplatin could theoretically be used in chemo-naive GCTs and support the further clinical evaluation of these agents in this setting. The mechanism of cross resistance to these drugs appears multifactorial.