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Inhibition
of human brain tumor cell growth by the anti-inflammatory drug, flurbiprofen
King
JG Jr, Khalili K
Laboratory
of Cancer Biology and Intervention, Center for Neurovirology and Cancer Biology,
College of Science and Technology, Temple University, Philadelphia,
Pennsylvania, PA 19122, USA
Despite
many efforts to alter the relentlessly aggressive progression of tumors of
neural origin, individuals bearing these tumors exhibit poor prognosis for
long-term survival.
In an attempt to find an effective treatment, we examined the efficacy of the
non-steroidal anti-inflammatory drug, flurbiprofen, to suppress the growth of
tumor cell lines derived from medulloblastoma and glioblastoma multiforme.
Results from cell proliferation assays have revealed that flurbiprofen
effectively inhibits the growth of various tumor cells in a dose-dependent
manner and causes a noticeable change in the progression of cells through cell
cycle stages.
Treatment of tumor cells with flurbiprofen reduced the number of cells in G1 and
G2, and significantly increased their numbers in S phase, suggesting that,
flurbiprofen accelerates G1/S entry, and/or delays cell exit from S to G2/M
stages.
Results from RNase protection assay and Western blot analysis showed that while
treatment of cells with flurbiprofen causes a minor change in the RNA level of
different cyclins, there is a significant decrease in the level of cyclin B
protein upon flurbiprofen treatment.
Examination of tumor suppressors by RNase protection technique showed a subtle
increase in the levels of several tumor suppressors upon flurbiprofen treatment.
Interestingly, at the protein level, p53 tumor suppressor was substantially
increased upon flurbiprofen treatment, yet the level of p21, a downstream target
for p53 remained unchanged.
Curiously, treatment of the cells with flurbiprofen enhanced the level of COX-2
expression.
Results from co-immunoprecipitation showed association of COX-2 with p53 in
tumor cells.
These observations suggest that the interaction of COX-2 with p53 may cause
p21-independent suppression of tumor cell growth upon flurbiprofen treatment.
PMID:
11687965 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11687965&dopt=Abstract
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