gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

Inhibition of in vitro and in vivo angiogenesis and tumour growth by a novel a5b1 inhibitor

Meeting Abstract

  • corresponding author presenting/speaker Carsten Dietz - Department of General Surgery, Philipps University, Marburg, Deutschland
  • Mohammed Soulaiman - Institute of Theoretical Surgery, Philipps University, Marburg
  • Elias Karakas - Department of General Surgery, Philipps University, Marburg
  • Sebastian Hennig - Institute of Theoretical Surgery, Philipps University, Marburg
  • G. Zahn - Jerini AG, Berlin
  • R. Stragies - Jerini AG, Berlin
  • Ilhan Celik - Institute of Theoretical Surgery, Philipps University, Marburg

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO507

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter:

Veröffentlicht: 20. März 2006

© 2006 Dietz et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen ( Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.



Introduction: The inhibition of the integrin a5b1 interferes with different angiogenic factors like VEGF, bFGF and other growth factors. In addition different angiogenesis processes like invasion, migration and proliferation of endothelial cells will be affected. Aim of the study was the survey of a5b1-inhibitor (JSM 6425) an its antiangiogenic and anti-tumour effects in vitro and in vivo.

Methods: Male immunodeficient mice ( SCID), 6-8 weeks old were used. BxPC-3 pancreatic cancer cells (5 x 106 in 0.2 ml RPMI 1640 medium were implanted subcutaneously (s.c.) in the dorsa of the mice (n=5/group). Tumour volume were measured every 3-5 days with the digital calliper. Mice were randomised in therapy and control groups when tumour size reached 100 +/- 20 mm3. Under isofluran anaesthesia mice were implanted intraperitonealy (i.p.) with mini-osmotic pumps (Alzet 2001; 1µl/h). Animals in the 3 therapy groups were treated continuously with 5, 0.5 und 0.05 mg/kg/day of JSM 6425. The control group received the diluent of JSM 6425 (placebo). Therapy was continued for a period of 21 days. At the end of the experiment tumours were explanted followed by immunohistological tests like microvessel density (MVD; CD31), proliferation (Ki-67) and apoptosis (TUNEL). Furthermore tumour cells (BxPC-3) und HUVEC´s (human umbilical vein endothelial cells) were investigated in vitro because of cytotoxicity, proliferation and apoptosis (Annexin V und TUNEL) (0,5 – 50 µM).

Results: During 21 days continuous therapy (i.p.) with JSM 6425 (5; 0.5 und 0.05 mg/kg/day) tumour growth was inhibited by 39 %, 19 % und 12 % versus placebo. During the whole experiment adverse side-effects or weight loss were absent in the animals. The tumours showed a significant (p<0.05) and dose depending inhibition of microvessel density MVD (CD31) and proliferating rate (Ki-67) without any significant effect on apoptosis rate. In vitro investigation revealed no significant effect on tumour cells but on HUVEC’s.

Summary: We found a dose dependent inhibition of tumour growth and significant inhibitory effects with regard to MVD and proliferation with JSM 6425 treatment. Optimal dosing and application route will be investigated in further experiments. With this spectrum of effectiveness and the absence of side-effects a5b1 integrin blockage might be a new and promising anti-tumour approach also in combination with other antiangiogenic substances or with chemotherapy and/or radiation.