Different effects of constitutive nitric oxide synthase and heme oxygenase on pulmonary or liver metastasis of colon cancer in mice.
It has recently been reported that not only endogenous nitric oxide (NO) but also carbon monoxide (CO) produced by heme oxygenase (HO) have many physiological functions. The objective of the present study was to determine whether endogenous NO or CO is involved in the experimental pulmonary or liver metastasis of colon cancer in mice. Intravenous or intrasplenic injection of colon 26 cells from a mouse colon adenocarcinoma cell line resulted in multiple pulmonary or liver metastases. NG-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthase (NOS), or zinc deuteroporphyrin 2, 4-bis glycol (ZnDPBG), a competitive inhibitor of HO, was administered to the mice only on the day of tumor inoculation. We assessed the number of tumor cells 24 h later and the outcome of metastases of the target organ. In the pulmonary metastasis model, L-NAME increased both the number of tumor cells 24 h later and outcome of metastases 18 days later, but did not have a significant effect on liver metastasis. On the other hand, metastasis to the liver, but not that to the lung, increased following administration of ZnDPBG. These results suggest that the activities of NOS and HO could influence experimental metastasis in an organ-specific manner.
Ishikawa
Takeshi
T
Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan.
Yoshida
Norimasa
N
Higashihara
Hiroshi
H
Inoue
Mamoru
M
Uchiyama
Kazuhiko
K
Takagi
Tomohisa
T
Handa
Osamu
O
Kokura
Satoshi
S
Naito
Yuji
Y
Okanoue
Takeshi
T
Yoshikawa
Toshikazu
T
D000818:Animals; D002248:Carbon Monoxide / Q000737:chemistry; D003110:Colonic Neoplasms / Q000473:pathology*; D003905:Deuteroporphyrins / Q000737:chemistry; D006419:Heme Oxygenase (Decyclizing) / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000556:secondary*; D008175:Lung Neoplasms / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000378:metabolism / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010974:Platelet Aggregation; D013997:Time Factors; D014407:Tumor Cells, Cultured
D003905:Deuteroporphyrins; C060750:zinc deuteroporphyrin IX 2,4-bis(glycol); D009569:Nitric Oxide; D002248:Carbon Monoxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D006419:Heme Oxygenase (Decyclizing); D019331:NG-Nitroarginine Methyl Ester