Inhibition of adhesion and proliferation of peritoneally disseminated tumor cells by pegylated catalase.
Hydrogen peroxide may aggravate the peritoneal dissemination of tumor cells by activating the expression of a variety of genes. In this study, we used pegylated catalase (PEG-catalase) to examine whether prolonged retention of catalase activity within the peritoneal cavity is effective in inhibiting peritoneal dissemination in mouse models. Murine B16-BL6 cells or colon 26 cells labeled with firefly luciferase gene were inoculated intraperitoneally into syngeneic mice. Compared with unmodified catalase, PEG-catalase was retained in the peritoneal cavity for a long period after intraperitoneal injection. A single injection of PEG-catalase just before tumor inoculation significantly reduced the number of the tumor cells at 1 and 7 days. The changes in the expression of molecules involved in the metastasis were evaluated by real time quantitative PCR analysis. Inoculation of the tumor cells increased the expression of intercellular adhesion molecule (ICAM)-1 in the greater omentum, which was inhibited by PEG-catalase. An injection of PEG-catalase at 3 days after tumor inoculation also reduced the number of the tumor cells, suggesting that processes other than the adhesion of tumor cells to peritoneal organs are also inhibited. Daily doses of PEG-catalase significantly prolonged the survival time of tumor-bearing mice. These results indicate that intraperitoneal injection of PEG-catalase inhibits the multiple processes of peritoneal dissemination of tumor cells by scavenging hydrogen peroxide in the peritoneal cavity.
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
Kuramoto
Yukari
Y
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
D000008:Abdominal Neoplasms / Q000473:pathology / Q000556:secondary; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002374:Catalase / Q000494:pharmacology* / Q000627:therapeutic use; D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007205:Indium Radioisotopes; D007274:Injections, Intraperitoneal; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000032:analysis; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects*; D009852:Omentum / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000556:secondary*; D011092:Polyethylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D011877:Radionuclide Imaging; D047368:Tumor Burden; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D000975:Antioxidants; C090509:Icam1 protein, mouse; D007205:Indium Radioisotopes; D009363:Neoplasm Proteins; D019010:Vascular Cell Adhesion Molecule-1; C070295:catalase-polyethylene glycol; D018799:Intercellular Adhesion Molecule-1; D011092:Polyethylene Glycols; D002374:Catalase; D053511:Matrix Metalloproteinase 14