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Vol. 280, Issue 1, 366-372, 1997
Unitat de Bioquímica, In Swiss 3T3 fibroblasts, aspirin inhibited proliferation induced by
the complete mitogenic factors platelet-derived growth factor (PDGF)
and bombesin. Aspirin decreased the maximum mitogenic effect of
bombesin without modifying the concentration necessary to obtain half
maximal DNA synthesis stimulation. In contrast, aspirin only decreased
mitogenesis at subsaturating PDGF concentrations. The effect of aspirin
was found to be concentration dependent. The half-maximal effect
occurred at approximately 150 µM. The maximal inhibition was obtained
when aspirin was added during the first hour after growth factor
addition. At this time, both PDGF and bombesin induced prostaglandin
E2 synthesis. PDGF induced much higher levels of
prostaglandin E2 than bombesin. The inhibitory effects of
aspirin on PDGF or bombesin-stimulated DNA synthesis were counteracted
by 280 nM prostaglandin E2. Aspirin effects were overcome
by agents that increase cellular cyclic adenosine monophosphate levels
but not by activation of protein kinase C. The significance of the
antiproliferative action of aspirin might be associated with
epidemiological data that show a reduced incidence of colorectal and
other cancers after aspirin treatment.
Copyright © by The American Society for Pharmacology and Experimental Therapeutics
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