We have investigated the antimetastatic effect of a new synthetic
lipid A analogue, of low endotoxicity,
DT-5461, against two highly metastatic tumor cell lines, L5178Y-ML25 T-
lymphoma and B16-BL6
melanoma cells in mice. Four intermittent i.v. administrations of
DT-5461 at intervals of 4 days resulted in a significant inhibition of liver
metastasis caused by i.v. injection of L5178Y-ML25 cells and lung
metastasis of B16-BL6 cells in the experimental
metastasis models. Intraperitoneal and
intranasal administrations as well as i.v. administration of
DT-5461 were also effective in preventing lung
metastasis of the
melanoma cells. Multiple administrations of
DT-5461 before the surgical excision of primary
tumors significantly reduced the number of lung colonies of
melanoma cells and primary
tumor size. Similarly, this treatment modality after the surgical excision of primary
tumors showed a greater reduction of lung
tumor colonies as compared with
lipopolysaccharide, a synthetic
lipid A (No. 506) and its analogue as well as untreated control in the spontaneous lung
metastasis model. Furthermore, the group that received
DT-5461 after the inoculation of
lymphoma or
melanoma cells showed significantly enhanced survival rate compared with the untreated control. These results suggested that
DT-5461 may be therapeutically useful for the inhibition of
tumor metastasis.