Interleukin‐2/sodium butyrate treatment cures rats bearing liver tumors after acquired 5‐fluorouracil resistance

We studied the effect of immunotherapy using recombinant interleukin-2 (rlL-2) in combination with a differentiating agent, sodium butyrate (NaBut), on experimental 5-fluorouracil (5-FU)-resistant liver metastasis from colorectal cancer in rats. For this purpose, we used direct liver injection of 5-FU resistant cells, PRObRI, in syngeneic BDIX rats to establish liver tumors. The growth of liver metastasis was followed before and after NaBut/rIL-2 treatment by magnetic resonance imaging (MRI). The presence of liver tumors was checked by MRI 7 days after tumor cell injection. Evaluable rats were then assigned randomly to a control and an experimental group. The different treatments were started on day 10 and administered intraperitoneally (i.p.). Combined NaBut/rIL-2 treatment followed by MRI on days 56 and 91 was shown both to significantly reduce the growth of liver tumors and to prevent extrahepatic spread. In addition, NaBut/rIL-2 treatment induced a complete regression in 50% of the rats which remained free of disease.