Abstract
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.
Footnotes
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Send reprint requests to: Dr. Joan Gil, Unitat de Bioquímica. Departament de Ciències Fisiològiques, Campus de Bellvitge, Universitat de Barcelona, Pabelló de Govern, 1° planta, C/Feixa Llarga s/n, 08907 Hospitalet de Ll, Barcelona, Spain.
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↵1 This work was supported by grants from “Maratóde TV3,” the “Fundació August Pi i Sunyer” (Campus de Bellvitge), the “Generalitat de Catalunya” (GRQ93/1131) and Quı́mica Farmacéutica Bayer S.A. (Division Consumer Care).
- Abbreviations:
- ASA
- aspirin
- DMEM
- Dulbecco’s modified Eagle’s medium
- EGF
- epidermal growth factor
- FCS
- fetal calf serum
- IBMX
- 3-isobutyl-l-methylxanthine
- NSAID
- nonsteroidal antiinflammatory drugs
- PDB
- phorbol 12,13-dibutyrate
- PDGF
- platelet-derived growth factor
- PG
- prostaglandin
- PGE2
- E2-type PG
- PGHS
- PG synthetase (E.C. 1.1499.1)
- PKC
- protein kinase C
- FAP
- familiar adenomatous polyposis
- Received February 14, 1996.
- Accepted September 12, 1996.
- The American Society for Pharmacology and Experimental Therapeutics
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