Inhibition of peritoneal dissemination of tumor cells by cationized catalase in mice.
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.
Hyoudou
Kenji
K
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Nishikawa
Makiya
M
Kobayashi
Yuki
Y
Mukai
Sakiko
S
Ikemura
Mai
M
Kuramoto
Yukari
Y
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
D000818:Animals; D002374:Catalase / Q000494:pharmacology / Q000627:therapeutic use*; D002412:Cations; D045744:Cell Line, Tumor; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010529:Peritoneal Cavity / Q000473:pathology / Q000502:physiology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D002412:Cations; D002374:Catalase