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Inhibition of human glioma cell growth by a
PHS-2 inhibitor, NS398, and a prostaglandin E receptor subtype EP1-selective
antagonist, SC51089
Matsuo M, Yoshida N, Zaitsu M, Ishii K, Hamasaki Y
Department of Pediatrics, Saga Medical School, Saga, Japan.
matsuo@post.saga-med.ac.jp
Prostaglandin H synthase (PHS) is a key enzyme in the synthesis of
prostaglandins (PGs).
Recently, enhanced expression of PHS-2 in brain tumors and the correlation
between the PHS-2 level and the histopathological grade of glioma has been
reported.
Furthermore, in vitro inhibition of glioma cell growth by a specific PHS-2
inhibitor, NS398, has been demonstrated.
It has also been shown that prostaglandin E2 (PGE2) contributes to colon
carcinogenesis by binding to the prostaglandin E receptor subtype EP1.
We therefore evaluated the effects of NS398 and two EP1 antagonists, SC51089 and
AH6809, on glioma cell lines.
To evaluate mechanisms of NS398's action, two glioma cell lines, a
PHS-2-positive cell line (KMG4) and a PHS-2-deficient cell line (A 172), were
used.
NS398 inhibited both the anchorage-dependent and -independent growth of glioma
cell lines regardless of PHS-2 expression, suggesting that some
PHS-2-independent mechanisms underlie the antineoplastic effect of NS398.
However, the antineoplastic effect was attenuated by the addition of PGE2, which
is one of the main products of PHS, suggesting the predominant mechanism is
PHS-dependent.
The EP1 antagonists, SC51089 and AH6809, inhibited the growth of glioma cell
lines in vitro.
Furthermore, NS398 or SC51089 slowed tumor growth in vivo, which was assessed
using KMG4 tumor xenografts on SCID mice.
PHS-2 inhibitors and EP1 antagonists might be useful in the prevention and/or
treatment of glioma.
PMID: 15015658 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15015658
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