gms | German Medical Science

27th German Cancer Congress Berlin 2006

German Cancer Society (Frankfurt/M.)

22. - 26.03.2006, Berlin

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

Meeting Abstract

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  • 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: http://www.egms.de/en/meetings/dkk2006/06dkk585.shtml

Published: March 20, 2006

© 2006 Rose et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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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.