The effect of recombinant human tumor necrosis factor-alpha on Ehrlich ascites tumor growth.

Abstract

We studied the antitumor effect of recombinant human tumor necrosis factor-alpha (rhTNF-alpha) on the intraperitoneal (i.p.) growth of Ehrlich ascites tumor (EAT) in Swiss albino male mice. The animals were treated with i.p. injection of rhTNF-alpha in doses of 5, 7.5, or 10 microg three times a week for 2 weeks, respectively, starting on the 4th day after the EAT inoculation. The effect of the cytokine was evaluated based on the following parameters: total ascites volume, packed cell volume, total packed cell volume, inhibitory growth rate, cellular population of EAT, morphological EAT cell changes, and mean survival time (MST). RhTNF-alpha in a dose of 5 microg had only a slight effect on MST and inhibitory growth rate (IGR). After a dose of 7.5 microg, an increased IGR (p < 0.01) was observed, but the animals did not live longer than the controls. After 7.5- and 10-microg doses (p < 0.001), the number of cells in EAT decreased significantly and enhanced cellular damage to EAT cells was found. In mice treated with 10 microg, a significant IGR (p < 0.001) was accompanied by enhancement of MST (p < 0.01). Although the 10 microg dose exerted a greater effect compared with the remaining doses, no complete regression was attained.