To inhibit peritoneal dissemination of
tumor cells by destroying
hydrogen peroxide,
ethylenediamine-conjugated
catalase (ED-
catalase), a cationized derivative, was injected into the peritoneal cavity of mice. ED-
catalase had about a 6-fold longer retention time within the cavity than unmodified
catalase. Peritoneal dissemination was evaluated after intraperitoneal inoculation of B16-BL6/Luc, a
melanoma clone stably expressing
firefly luciferase, by measuring
luciferase activity. An
intraperitoneal injection of ED-
catalase just before
tumor inoculation significantly reduced the number of
tumor cells in peritoneal organs.
Catalase was less effective, confirming the importance of the retention of the
enzyme within the cavity for the inhibition. ED-
catalase injected 3 days after
tumor inoculation was also effective in inhibiting
tumor growth. A real-time quantitative PCR analysis revealed that ED-
catalase significantly suppressed the expression of
intercellular adhesion molecule-1. Daily dosing of ED-
catalase for 7 days significantly prolonged the survival of
tumor-bearing mice. These findings indicate that ED-
catalase, which is retained for a long time within the peritoneal cavity, is highly effective in inhibiting the adhesion and proliferation of peritoneally disseminated
tumor cells, and in increasing the survival of
tumor-bearing mice.