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Inhibition of Ehrlich ascites tumor in vivo by PAF-antagonists
Abstract:
Several lines of evidence support that PAF modulates the inflammatory and immune responses, and that tumors may inhibit both these processes. In the present study we analysed the effect of PAF antagonists on the growth of Ehrlich Ascites Tumor (EAT) in vivo. Mice were inoculated intraperitoneally with 1 x 10(3) EAT cells and the tumor growth evaluated by counting the number of peritoneal cells, 1,6 and 10 days after tumor implantation. BN 52021 was administered intraperitoneally, intravenously or subcutaneously once or twice a day, at 1.0, 2.5, 5.0 and 20.0 mg/kg. Control animals received 0.1 ml of the vehicle in the same schedule. It was found that i.p. and i.v. administration of BN 52021 (5 mg/kg, twice a day) significantly inhibited EAT growth (80.8% and 56.0% respectively). Other routes and doses were less effective. Another PAF antagonist, SRI 63441 (5 mg/kg, i.p., twice a day) also inhibited EAT growth (80.4%). The BN 52021 added to EAT cells in culture, at concentration of 10(-3) and 10(-4) M, did not affect the viability and proliferation of tumors cells. In an attempt to understand the mechanism of this inhibition, we analyzed the peritoneal macrophages for spreading ability and H2O2 release. It was found that 24 h after tumor implantation there was an increase in the spreading ability of peritoneal macrophages (75%) and that, as the tumor grew, the spreading index fell to control levels ( less than 10%). (5 mg/kg/twice a day) the spreading remained elevated (50-60%) at all the times examined. Release of H2O2, measured by horseradish peroxidase-phenol red oxidation, was below detectable levels throughout tumor growth.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Platelet-activating factor (PAF) antagonists, BN 52021 and SRI 63441, significantly inhibited Ehrlich Ascites Tumor (EAT) growth in mice. These compounds did not directly impact tumor cell viability but modulated macrophage spreading ability, suggesting an immune-mediated anti-tumor effect.
Area of Science:
- Immunology
- Pharmacology
- Oncology
Background:
- Platelet-activating factor (PAF) plays a role in inflammatory and immune responses.
- Tumors can suppress these immune and inflammatory processes.
- Understanding how to modulate these responses is crucial for cancer therapy.
Purpose of the Study:
- To investigate the in vivo effect of PAF antagonists on Ehrlich Ascites Tumor (EAT) growth.
- To explore the potential anti-tumor mechanisms of PAF antagonists.
Main Methods:
- Ehrlich Ascites Tumor (EAT) cells were implanted in mice.
- PAF antagonists (BN 52021, SRI 63441) were administered via various routes and doses.
- Tumor growth was assessed by counting peritoneal cells.
- Macrophage spreading ability and hydrogen peroxide (H2O2) release were analyzed.
Main Results:
- Intraperitoneal and intravenous administration of BN 52021 (5 mg/kg, twice daily) significantly inhibited EAT growth (80.8% and 56.0%, respectively).
- SRI 63441 (5 mg/kg, intraperitoneally, twice daily) also demonstrated significant EAT growth inhibition (80.4%).
- BN 52021 did not affect tumor cell viability or proliferation in vitro, but maintained elevated peritoneal macrophage spreading ability in vivo.
Conclusions:
- PAF antagonists can effectively inhibit EAT tumor growth in vivo.
- The anti-tumor effect appears to be mediated through modulation of the host immune response, specifically macrophage function, rather than direct cytotoxicity to tumor cells.