Interferon-beta inhibits liver metastases from murine colon 26 carcinoma and its highly metastatic variant.
OBJECTIVE
The antitumor effects of Interferon-beta (IFN-beta) are due to its direct inhibition of cell proliferation, immunostimulatory activity, and the inhibition of angiogenesis. We investigated the mechanism of the effects of IFN-beta on a murine colon 26 cell line (CT 26) and its highly metastatic variant (L5).


METHODS
We examined its inhibitory effects on cell proliferation in vitro and the development of liver metastases in vivo.


RESULTS
The proliferation of CT 26 in vitro was inhibited by IFN-beta in a dose- and time-dependent manner. The number of metastases was reduced in mice inoculated with CT 26 (P<0.01) and L5 (P<0.01) on Day 14 after treatment with IFN-beta. The median survival rate of the mice inoculated with L5 administered IFN-beta every other day, or every day was higher than in the control group (P<0.05). A dorsal air sac assay demonstrated that IFN-beta inhibited angiogenesis in mice inoculated with CT 26, but the effects disappeared with aminoguanidine, an inducible nitric oxide synthase inhibitor.


CONCLUSIONS
These results showed that IFN-beta directly inhibits the proliferation of CT 26. In addition, the in vivo experiments suggested that IFN-beta might effectively inhibit liver metastases.
Kohashi
Shigechika
S
Department of Gastroenterological and General Surgery, Hokkaido University School of Medicine, N15-W7 Kita-ku, Sapporo, 060-8638, Japan.
Sato
Yuji
Y
Fukushima
Tsuyoshi
T
Shomura
Hiroki
H
Oshima
Takahiro
T
Bairun
Sun
S
Kondo
Masao
M
Une
Yoshie
Y
Nishihira
Jun
J
Todo
Satoru
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D007370:Interferon Type I / Q000494:pharmacology / Q000627:therapeutic use*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins
D000970:Antineoplastic Agents; D007370:Interferon Type I; D011994:Recombinant Proteins