[Leflunomide reduces the angiogenesis score and tumor growth of subcutaneously implanted colon carcinoma cells in the mouse model].
BACKGROUND
The inhibition of tumorangiogenesis may be of importance in the additive treatment of various cancers. Leflunomide, a drug which has been approved in Germany for the therapy of rheumatoid arthritis, inhibits the activity of several growth factors in vitro. The aim of this study was to investigate the effects of the drug on tumor angiogenesis in a nude mouse model.


METHODS
A total of 40 nude mice were injected with human colon carcinoma cells. Following randomization in 4 groups, therapy started on day five. Group 1 was treated daily with orally administered Leflunomide (35 mg/kg) dissolved in 1.5% Carboxymethylcellulose (CMC). Group 2 served as a control group and received 1 ml CMC orally per day. The animals of group 3 were treated daily with 35 mg Leflunomide/kg KG and 500 mg Uridine/kg dissolved in 1 ml Nacl 0.9% intraperitoneally. The 4th group again served as a control group and received only 500 mg Uridine/kg intraperitoneally each day. The main outcome criterion was the angiogenesis score (AS). In addition, the tumor volume and tumor weight were also assessed. The AS was determined by immunohistochemistry using an antibody against factor VIII related antigen.


RESULTS
All animals tolerated the procedure well. In the Leflunomide and the Leflunomide/Uridine group the angiogenesis score (p < 0.01), the tumor volume (p < 0.01) and the tumor weight (p < 0.01) were lower compared to the respective control groups.


CONCLUSIONS
The administration of Leflunomide leads to a significant reduction of tumor weight and tumor volume following subcutaneous injection of human colon carcinoma cells in a nude mouse model. This could be due to the reduction of tumor angiogenesis. Following further experimental and clinical studies, Leflunomide may come to play a role in the additive treatment of colonic carcinoma.
Mall
J W
JW
Klinik für Allgemein-, Visceral-, Gefäss- und Thoraxchirurgie, Charité, Campus Mitte, Schumannstrasse 20/21, 10117 Berlin. julianmall@hotmail.com
Myers
J A
JA
Xu
X
X
Saclarides
T J
TJ
Philipp
A W
AW
Pollmann
C
C
D000284:Administration, Oral; D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D002455:Cell Division / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000473:pathology; D019073:HT29 Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007274:Injections, Intraperitoneal; D007555:Isoxazoles / Q000494:pharmacology*; D000077339:Leflunomide; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011897:Random Allocation; D014529:Uridine / Q000494:pharmacology
D007555:Isoxazoles; D000077339:Leflunomide; D014529:Uridine