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 (rIL-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.
Cordel
S
S
INSERM U419, Institut de Biologie, Nantes, France.
Dupas
B
B
Douillard
J Y
JY
Meflah
K
K
D000818:Animals; D002087:Butyrates / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D008279:Magnetic Resonance Imaging; D008297:Male; D009368:Neoplasm Transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage
D002087:Butyrates; D007376:Interleukin-2; D011994:Recombinant Proteins; D005472:Fluorouracil