Klin Padiatr 2004; 216 - 56
DOI: 10.1055/s-2004-828601

Doxorubicin reduces telomerase activity in a human Ewing-Xenograft tumor

B Winter 1, C Lanvers-Kaminsky 2, S Koling 2, B Frodermann 3, Y Braun 3, KL Schäfer 3, RI Diallo 3, S Könemann 1, J Boos 2, N Willich 1, C Poremba 3, A Schuck 1
  • 1Department of Radiotherapy, University hospital, Münster, Germany
  • 2University children's hospital, Department of Paediatric Haematology and Oncology, Münster, Germany
  • 3Department of Pathology, Heinrich Heine University, Düsseldorf, Germany

Aim: For its almost selective expression in human tumours telomerase is a promising target for cancer treatment. We evaluated the effects of doxorubicin (DOX) on telomerase in the human Ewing sarcoma cell line STA-ET-1 in vitro and in nude mice in vivo.

Methods: In vitro toxicity was determined by the MTT-assay. Tumour xenografts were analysed for proliferation, necrosis, and apoptosis by MIB-, HE-staining and TUNEL assay. Telomerase activity (TA) was examined by the TRAP assay and hTERT mRNA expression by real-time PCR.

Results: In vitro along with growth inhibition DOX treatment reduced TA but the employed concentrations did not directly affect TA. At non-toxic concentrations doxorubicin increased TA about 2 times.

In xenografts treated with 17.5mg/kg DOX i.p. TA declined to 60% after 72h. The expression of hTERT mRNA dropped to 25% after 72h and increased thereafter. After 264h and 366h TA, and hTERT again reached initial values. hTERT expression correlated well with the rate of proliferating cells by not with TA, apoptosis or necrosis.

Conclusion: The results suggest that the reduction of TA in STA-ET-1 is due to complex changes within the DOX damaged cell that involve the repression of hTERT expression.

supported by the IZKF Münster 3H2