High-dose, short-term, anti-inflammatory treatment with dexamethasone reduces growth and augments the effects of 5-fluorouracil on dimethyl-alpha- benzanthracene-induced mammary tumors in rats

• Objective. To evaluate the effects of dexamethasone (DXM) alone or in combination with 5-fluorouracil (5-FU) on dimethyl-alpha-benzanthracene (DMBA)-induced mammary tumors in rats. Material and methods. Female Sprague-Dawley rats were divided into 4 groups receiving: 1) saline (controls), 2) DXM (3 mg/kg), 3) 5-FU (1.5 mg/kg) and 4) DXM and 5-FU combined. The drugs were given i.p. every day for 4 days. Interstitial fluid pressure (Pif) and tumor growth were determined in all tumors on days 1, 5 and 7 using the "wick-in-the needle'' technique and by external size measurements, respectively. Vessel density and inflammatory cell infiltration of tumor tissue were analyzed by immunohistochemistry. Results. DXM treatment significantly retarded tumor growth and reduced Pif. Treatment with a combination of DXM and 5-FU reduced tumor size significantly more than any of the agents alone (p < 0.01 - 0.001). Enhanced uptake of 5-FU by DXM treatment was demonstrated by microdialysis. There were no differences in the density of CD31-positive vessels after DXM or 5-FU treatment, but inflammatory cell infiltration of tumor tissue was significantly reduced after DXM treatment. Conclusions. Our data suggest that DXM may be beneficial as an adjuvant to chemotherapy in the treatment of mammary cancer by increasing the uptake of 5-FU in the tumor.

Nyckelord

dexamethasone

5-FU

inflammatory cell infiltration

interstitial fluid pressure

tumor growth

vessel density

MEDICINE

MEDICIN

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