PEGylated catalase prevents metastatic tumor growth aggravated by tumor removal.
Although surgical removal is a primary option for treating tumors, it can lead to the increased growth of metastatic tumors. Because surgical procedures may generate reactive oxygen species (ROS), known promoters of tumor metastasis and growth, we investigated whether PEGylated catalase (PEG-catalase, plasma half-life of 13.6 h) was able to prevent this after surgical removal of a footpad tumor in mice. Murine melanoma cells labeled with the firefly luciferase gene were used to monitor the distribution of tumor cells. After inoculation into the footpad, tumor cells were found in the lung, and the number increased with time. The surgical removal of the footpad tumor significantly (p < 0.05) increased the number of metastatic tumor cells and the level of plasma lipoperoxides. An intravenous injection of PEG-catalase significantly (p < 0.05) suppressed the metastatic tumor growth as well as the peroxidation. Quantitative RT-PCR and Western blot analyses indicated that PEG-catalase markedly reduced the increase in the expression of epidermal growth factor receptor. These findings indicate that the removal of tumor produces ROS, which then aggravate metastatic tumor growth by activating several growth factors. PEG-catalase can effectively prevent this metastatic tumor growth by detoxifying the ROS.
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
Umeyama
Yukari
Y
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
D000818:Animals; D015153:Blotting, Western; D002374:Catalase / Q000627:therapeutic use*; D048888:Fireflies / Q000201:enzymology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008156:Luciferases / Q000378:metabolism; D008175:Lung Neoplasms / Q000201:enzymology / Q000517:prevention & control* / Q000556:secondary; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000601:surgery; D051379:Mice; D008810:Mice, Inbred C57BL; D016877:Oxidants / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
D016877:Oxidants; D017382:Reactive Oxygen Species; C070295:catalase-polyethylene glycol; D011092:Polyethylene Glycols; D006861:Hydrogen Peroxide; D002374:Catalase; D008156:Luciferases