PEGylated catalase prevents metastatic tumor growth aggravated by tumor removal
PEGylated catalase prevents metastatic tumor growth aggravated by tumor removal
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DOI：
10.1016/j.freeradbiomed.2006.08.004
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发表时间：
2006-11-01
影响因子：
7.4
通讯作者：
Hashida, Mitsuru
中科院分区：
文献类型：
--
作者：
Hyoudou, Kenji;Nishikawa, Makiya;Hashida, Mitsuru
虽然手术切除是治疗肿瘤的主要选择，但它可能导致转移性肿瘤的增加。由于外科手术可能产生活性氧（ROS），这是已知的肿瘤转移和生长的促进剂，我们研究了聚乙二醇化过氧化氢酶（peg -过氧化氢酶，血浆半衰期为13.6 h）是否能够在手术切除小鼠脚垫肿瘤后防止这种情况的发生。用萤火虫荧光素酶基因标记的小鼠黑色素瘤细胞监测肿瘤细胞的分布。接种足垫后，肺内可见肿瘤细胞，肿瘤细胞数量随时间增加而增加。足底肿瘤切除后，肿瘤转移细胞数量及血浆脂过氧化物水平显著升高（p < 0.05）。静脉注射peg -过氧化氢酶能显著抑制转移瘤的生长（p < 0.05）和过氧化作用。定量RT-PCR和Western blot分析表明，peg -过氧化氢酶显著降低了表皮生长因子受体表达的增加：这些结果表明，肿瘤的切除产生ROS， ROS通过激活多种生长因子而加剧转移性肿瘤的生长。peg -过氧化氢酶可以通过解毒活性氧有效地阻止这种转移性肿瘤的生长。(c) 2006爱思唯尔公司版权所有。
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. (c) 2006 Elsevier Inc. All rights reserved.