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Synergy
between angiostatin and endostatin: inhibition of ovarian cancer growth
Yokoyama
Y, Dhanabal M, Griffioen AW, Sukhatme VP, Ramakrishnan S
Department
of Pharmacology, University of Minnesota, Minneapolis 55455, USA
Ovarian
cancer is the leading cause of fatality among gynecological malignancies.
Ovarian cancer growth is angiogenesis-dependent, and an increased production of
angiogenic growth factors such as vascular endothelial growth factor is
prognostically significant even during early stages of the disease.
Therefore, we investigated whether antiangiogenic treatment can be used to
inhibit the growth of ovarian cancer in an experimental model system.
Mouse angiostatin (kringle 1-4) and endostatin were expressed in yeast.
Purified angiostatin and endostatin were then used to treat established ovarian
cancers in athymic mice.
These studies showed that both angiostatin and endostatin inhibited tumor
growth.
However, angiostatin treatment was more effective in inhibiting ovarian cancer
growth when compared with endostatin in parallel experiments.
Residual tumors obtained from angiostatin- and endostatin-treated animals showed
decreased number of blood vessels and, as a consequence, increased apoptosis of
tumor cells.
Subsequently, the efficacy of a combined treatment with angiostatin and
endostatin was investigated.
In the presence of both angiostatic proteins, endothelial cell proliferation was
synergistically inhibited.
Similarly, a combination regimen using equal amounts of angiostatin and
endostatin showed more than additive effect in tumor growth inhibition when
compared with treatment with individual angiostatic protein.
These studies demonstrate synergism between two angiostatic molecules and that
antiangiogenic therapy can be used to inhibit ovarian cancer growth.
PMID:
10786683 [PubMed - indexed for MEDLINE]
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