Antitumor effect of recombinant human interferon-beta and interferon-gamma in combination against human colon cancer cell line in vitro and in nude mice.
The antiproliferative activity of recombinant human interferon (rIFN)-beta and rIFN-gamma, alone or in combination, against a human colon cancer cell line (RPMI 4788) was examined in vitro and in nude mice. rIFN-beta and rIFN-gamma interacted synergistically in vitro. In experimental pulmonary metastasis and intraabdominal carcinomatosis in nude mice, rIFN-beta and rIFN-gamma were administered iv and ip, respectively, alone or in combination, for 10 consecutive days beginning 2 days after RPMI 4788 cells were inoculated. In both models, rIFN-beta and rIFN-gamma alone had significant antitumor effects compared with the saline-control group. Combined administration of rIFN-beta and rIFN-gamma resulted in marked antitumor effects. In the pulmonary metastasis model, there were no pulmonary metastatic nodules in the group treated with the combination of rIFN-beta and rIFN-gamma (P less than 0.001), while there were 324.6 +/- 83.1 (mean +/- SD) nodules in the control group. In the intraabdominal carcinomatosis model, the mean survival time was 114.0 +/- 8.2 days (P less than 0.01) for the combination therapy group, but only 41.8 +/- 5.6 days for the control group. These results suggest that combined treatment with rIFN-beta and rIFN-gamma might be a promising therapy for pulmonary metastasis and intraabdominal carcinomatosis of human cancers.
D000008:Abdominal Neoplasms / Q000628:therapy; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology; D004338:Drug Combinations; D004357:Drug Synergism; D007370:Interferon Type I / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000008:administration & dosage*; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000473:pathology
D004338:Drug Combinations; D007370:Interferon Type I; D011994:Recombinant Proteins; D007371:Interferon-gamma