gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

Hypoxia inducible transcription factor HIF-2a interferes with cisplatin induced cell death in adenocarcinoma cells in vitro

Meeting Abstract

  • corresponding author presenting/speaker Frank Rose - University of Giessen and Marburg, Deutschland
  • Bastian Eul - University of Giessen and Marburg
  • Florentine Kamlah - University of Giessen and Marburg
  • Hanxiang An - University of Giessen and Marburg
  • Friedrich Grimminger - University of Giessen and Marburg
  • Rita Engenhart-Cabillic - University of Giessen and Marburg
  • Werner Seeger - University of Giessen and Marburg
  • Jörg Hänze - University of Giessen and Marburg

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO475

The electronic version of this article is the complete one and can be found online at:

Published: March 20, 2006

© 2006 Rose et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Hypoxia is known to affect tumor progression and drug resistance. This study investigated the possible significance of hypoxia-inducible factors (HIFs) in hypoxic adenocarcinoma (A549) cells, exposed to cisplatin chemotherapy. In normoxic A549 cells, cisplatin (0.1µg/µl) reduced cell survival to 32,3% ± 5,1%, as assessed by MTT assay. In hypoxia, cisplatin exerted only a minor MTT-decrease of 9,16% ± 6%. For analyzes of interaction of cisplatin with hypoxia-induced signal transduction we measured activation of the hypoxia responsive element (HRE), the binding domain of the hypoxia transcription factors (HIF-1a and HIF-2a). Cisplatin demonstrated activation of HRE both in normoxia and hypoxia. Vice versa, we analyzed the effect of HIF inhibition on cisplatin toxicity. Specific inhibition of HIF-2a by synthetic siRNA significantly increased the toxicity of cisplatin, whereas suppression of HIF-1a by siRNA or a random siRNA control had no effect. Thus, we conclude that hypoxia suppresses the response to cisplatin in A549 cells through activation of HIF-2. Targeting HIF-2 by RNA interference may represent a new strategy to improve the response to cisplatin in hypoxic tumor cells.