Antitumor effect of a splenic injection of 5-fluorouracil on metastatic liver cancer in mice.
The regional administration of 5-fluorouracil (5-FU) has been the fundamental therapy against liver metastases for the improvement of patient prognosis; however, there have been few reports about the immunological effects of this agent. It is also unknown whether it affects the spleen, one of the major lymphoid organs. The objective of the present study was to determine the immunological effect of an intrasplenic injection of 5-FU against liver metastases. We investigated the effect of an intrasplenic injection of 5-FU on the formation of experimental liver metastasis resulting from an intraportal vein injection of colon 26 carcinoma cells in BALB/c mice and elucidated some of the underlying mechanisms involving the effects of this on cellular immunity. Liver metastases were significantly diminished by the splenic injection of 5-FU, particularly in comparison with the portal injection or systemic administration. This was followed by augmentation of the interleukin-12 (IL-12) level in the spleen and activation of hepatic mononuclear cells. In those cells, NK1.1+ (NKT) cells played a central role against metastases. A splenic injection of 5-FU is more effective on the involution of liver metastases than portal or systemic injection. This effect may be attributed to the augmentation of the IL-12 level in the spleen and of NKT cells in the liver rather than to the original effect of 5-FU, which is the so-called inhibition of DNA synthesis.
Kanoh
Kenichi
K
Department of General Surgical Science, Gunma University, Graduate School of Medicine, Maebashi, Japan. kenkanoh@showa.gunma-u.ac.jp
Shimura
Tatsuo
T
Suzuki
Hideki
H
Nomoto
Kenichi
K
Asao
Takayuki
T
Kuwano
Hiroyuki
H
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D007267:Injections; D018664:Interleukin-12 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism; D008099:Liver / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000187:drug effects; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000964:Antimetabolites, Antineoplastic; D018664:Interleukin-12; D005472:Fluorouracil