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.