Modulation of Cytokines Production by Indomethacin Acute Dose during the Evolution of Ehrlich Ascites Tumor in Mice

The aim of the present study was to investigate the influence of a nonselective COX1/COX2 inhibitor (indomethacin) on tumor growth of Ehrlich Ascites Tumor (EAT) in mice, using as parameters the tumor growth and cytokine profile. Mice were inoculated with EAT cells and treated with indomethacin. After 1, 3, 6, 10, and 13 days the animals were evaluated for the secretion of TNFα, IL-1α, IL-2, IL-4, IL-6, IL-10, and IL-13 and PGE2level in peritoneal cavity. The results have shown that EAT induces PGE2production and increases tumor cells number from the 10th day. The cytokine profile showed EAT induces production of IL-6 from 10th day and of IL-2 on 13th day; the other studied cytokines were not affected in a significant way. The indomethacin treatment of EAT-bearing mice inhibited the tumor growth and PGE2synthesis from the 10th day. In addition, the treatment of EAT-bearing mice with indomethacin has stimulated the IL-13 production and has significantly inhibited IL-6 in the 13th day of tumor growth. Taken together, the results have demonstrated that EAT growth is modulated by PGE2and the inhibition of the tumor growth could be partly related to suppression of IL-6 and induction of IL-13.

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Cytokine profile of Ehrlich ascites tumor treated withBothrops jararacavenom

Mediators of Inflammation ◽

10.1080/0962935029000041 ◽

2002 ◽

Vol 11 (4) ◽

pp. 197-201 ◽

Cited By ~ 16

Author(s):

Reinaldo J. da Silva ◽

Márcia G. da Silva ◽

Lízia C. Vilela ◽

Denise Fecchio

Keyword(s):

Tumor Growth ◽

Antitumor Effect ◽

Cytokine Profile ◽

Ehrlich Ascites Tumor ◽

Enzyme Linked Immunosorbent Assay ◽

Ascites Tumor ◽

Ehrlich Ascites ◽

Tnf Α ◽

Cytokine Levels ◽

Eat Cells

We previously demonstrated thatBothrops jararacavenom (BjV) has an antitumor effect on Ehrlich ascites tumor (EAT) cells and induces an increase of polymorphonuclear leukocytes in early stages of tumor growth. It has been reported that this venom presents an important inflammatory effect when inoculated in animal models and in human snakebites, and that cytokine levels have been detected in these cases. To evaluate whether the cytokines can be involved with the suppression of the tumoral growth, we evaluate the cytokine profile in the peritoneal cavity of mice inoculated with EAT cells and treated withBjV. Swiss mice were inoculated with EAT cells by the intraperitoneal route and treated withBjV venom (0.4 mg/kg, intraperitoneally), on the 1st, 4th, 7th, 10th, and 13th day. Mice were evaluated for cytokine levels on the 2nd, 5th, 8th, 11th and 14th day. Analysis was performed using an enzyme-linked immunosorbent assay for interleukin (IL)-1α, IL-2, IL-4, IL-6, IL-10, IL-13, and tumor necrosis factor-α (TNF-α) levels in the peritoneal washing supernatant. Results were analyzed statistically by the Kruskal-Wallis and Dunn's tests at the 5% level of significance. We observed that EAT implantation induces IL-6 production on the 11th and 14th days of tumor growth, IL-10 on the 11th day and TNF-α on the 14th day. The treatment withBjV suppresses production of these cytokines. In addition, IL-13 was produced by animals that were inoculated only with venom on the 11th and 14th days, and by the group inoculated with EAT cells and treated with venom on the 2nd and 14th days. Furthermore, we suggest that the IL-6 detected in the present study is produced by the EAT cells and the suppression of its production could be associated with the antitumor effect ofBjV.

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Further Investigations on the p-Nitrophenylphosphatase Activity of Intact Ehrlich Ascites Tumor Cells

Zeitschrift für Naturforschung C ◽

10.1515/znc-1978-3-410 ◽

1978 ◽

Vol 33 (3-4) ◽

pp. 227-230 ◽

Cited By ~ 1

Author(s):

Reiner Merz ◽

Monika Löffler ◽

Friedhelm Schneider

Keyword(s):

Tumor Cells ◽

Active Sites ◽

Ehrlich Ascites Tumor ◽

Ehrlich Ascites Tumor Cells ◽

Ascites Tumor ◽

Intact Cells ◽

Blocking Agents ◽

Ehrlich Ascites ◽

Eat Cells ◽

Hydrolysis Of

The substrate specificity and the effects of nucleotides and SH-blocking agents on the p-nitro- phenylphosphatase activity of intact Ehrlich ascites tumor cells (EAT) cells were studied, ᴅʟ-β- Glycerophosphate, o-phosphoethanolamine, cholinephosphate, glucose-6-phosphate, o-carboxyphenyl- phosphate,, phosphoenolpyruvate and AMP were not attacked by intact cells. ATP > GTP > UTP > PPi > pNPP were cleaved with decreasing velocity. A stimulation of the cleavage of p-NPP by the following nucleotides was observed with decreasing effectivity: ATP > ADP > GTP > UTP; AMP was ineffective. The phosphatase activity was not affected by malate, tartrate and glutathion disulfide. The SH blocking agents diamide and thimerosal were more effective inhibitors of the pNPPase than of the ATPase activity, whereas the hydrolysis of ATP is more affected by the ATP analog adenylylimidodiphosphate. The present data are best compatible with a double headed enzyme: Both active sites interact with ATP, only one is active against p-NPP and sensitive against SH-blocking agents.

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Heterotransplantation of Ehrlich Ascites Tumor Cells in Rats Pre-Treated with Cytostatics and Antimetabolites

Zeitschrift für Naturforschung B ◽

10.1515/znb-1970-1022 ◽

1970 ◽

Vol 25 (10) ◽

pp. 1175-1179 ◽

Cited By ~ 1

Author(s):

Emanuil Emanuilov ◽

Evgeny Golovinsky

Keyword(s):

Tumor Growth ◽

Tumor Cell ◽

Tumor Cells ◽

Dose Dependence ◽

Ehrlich Ascites Tumor ◽

Ehrlich Ascites Tumor Cells ◽

Ascites Tumor ◽

Tumor Cell Population ◽

Ehrlich Ascites ◽

Progressive Growth

Pre-reatment of rats with various doses of cytostatics and antimetabolites (cyclophosphamide, mitomycin-C, 6-mercaptopurine, 6-azauridine and 5-azaorotic acid) permits successful heterotransplantation of Ehrlich ascites tumor, as indicated by the progressive growth of the tumor cell population. Experiments with cyclophosphamide suggest a direct dose dependence of the rate of tumor growth in heterologous recipients.

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