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Antitumor effect to IL‐12 administration into the portal vein on murine liver metastasis
Author(s) -
Su Wei,
Kitagawa Toru,
Ito Toshinori,
Oyama Tsukasa,
Lee Chun Man,
Kim YongKook,
Matsuda Hikaru
Publication year - 2002
Publication title -
journal of hepato‐biliary‐pancreatic surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.63
H-Index - 60
eISSN - 1868-6982
pISSN - 0944-1166
DOI - 10.1007/s005340200063
Subject(s) - medicine , spleen , metastasis , portal vein , intraperitoneal injection , tail vein , gastroenterology , saline , cancer , in vivo , biology , microbiology and biotechnology
Abstract Background/Purpose Interleukin (IL)‐12 has been shown to possess potent antitumor activity, and an antitumor effect of systemic IL‐12 administration has been reported in liver metastasis models. Methods In this study, we examined the usefulness of local IL‐12 administration into the portal system in the treatment of liver metastasis. First, we confirmed the antitumor effect of recombinant IL‐12 (rIL‐12) on MC‐38 tumors in an intracutaneous model. In the murine liver metastasis model, 1 × 10 5 of MC‐38 cells were injected into the portal vein on day 0, and the spleen was transpositioned subcutaneously for administration of rIL‐12 continually into the portal system. From days 3 to 7, 0.1μg rIL‐12 was administered intraperitoneally or intrasplenicly, while Hanks' Balanced Salf Solution (HBSS) was injected intrasplenicly in the control group. Results The liver weight in the rIL‐12 intraperitoneal treatment group (1.88 ± 0.37 g) and that in the rIL‐12 intrasplenic treatment group (1.43 ± 0.21 g) were significantly less than that in the HBSS group (2.86 ± 0.74 g; P < 0.05). The numbers of metastatic nodules in the rIL‐12 intraperitoneal treatment group (22.3 ± 17.1) and in the rIL‐12 intrasplenic treatment group (12.4 ± 13.8) were significantly less than that in the HBSS group (137.1 ± 44.9; P < 0.05). Complete regression of the tumor was observed in one of six mice in the rIL‐12 intrasplenic treatment group. This antitumor effect of rIL‐12 on MC‐38 liver metastasis was not observed in interferon (IFN)‐γ knockout mice. Intraportal administration of IL‐12‐transduced fibroblasts, which were syngeneic to C57BL/6 mice, had an antitumor effect in the MC‐38 liver metastasis model. Conclusions These results suggested that the local administration of IL‐12 into the portal system would be a useful strategy for the treatment of liver metastasis.