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Rapamycin
inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of
vascular endothelial growth factor
Guba M, von
Breitenbuch P, Steinbauer M, Koehl G, Flegel S, Hornung M, Bruns CJ, Zuelke C,
Farkas S, Anthuber M, Jauch KW, Geissler EK
Department
of Surgery, University of Regensburg, Regensburg, Germany.
markus.guba@klinik.uni-regensburg.de
Conventional
immunosuppressive drugs have been used effectively to prevent immunologic
rejection in organ transplantation.
Individuals taking these drugs are at risk,
however, for the development and recurrence of cancer.
In the present study we show that the new immunosuppressive drug rapamycin (RAPA)
may reduce the risk of cancer development while simultaneously providing
effective immunosuppression.
Experimentally, RAPA inhibited metastatic tumor growth and angiogenesis in in
vivo mouse models.
In addition, normal immunosuppressive doses of RAPA effectively controlled the
growth of established tumors.
In contrast, the most widely recognized immunosuppressive drug, cyclosporine,
promoted tumor growth.
From a mechanistic perspective, RAPA showed antiangiogenic activities linked to
a decrease in production of vascular endothelial growth factor (VEGF) and to a
markedly inhibited response of vascular endothelial cells to stimulation by VEGF.
Thus, the use of RAPA, instead of cyclosporine, may reduce the chance of
recurrent or de novo cancer in high-risk transplant patients.
PMID:
11821896 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11821896&dopt=Abstract
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