Inhibition of adhesion and proliferation of peritoneally disseminated tumor cells by pegylated catalase
Inhibition of adhesion and proliferation of peritoneally disseminated tumor cells by pegylated catalase
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DOI：
10.1007/s10585-006-9036-8
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发表时间：
2006-11-01
影响因子：
4
通讯作者：
Hashida, Mitsuru
中科院分区：
文献类型：
--
作者：
Hyoudou, Kenji;Nishikawa, Makiya;Hashida, Mitsuru
过氧化氢可能通过激活多种基因的表达而加重肿瘤细胞的腹膜播散。在这项研究中，我们使用聚乙二醇化过氧化氢酶（PEG-过氧化氢酶），以检查是否在腹腔内的过氧化氢酶活性的长期保留是有效的抑制腹膜传播的小鼠模型。将萤火虫荧光素酶基因标记的小鼠B16-BL 6细胞或结肠26细胞接种于同系小鼠腹腔内。与未修饰的过氧化氢酶相比，PEG-过氧化氢酶在腹腔注射后在腹腔内保留较长时间。在肿瘤接种前单次注射PEG-过氧化氢酶在第1天和第7天显著减少了肿瘤细胞的数量。通过真实的实时定量PCR分析来评估参与转移的分子的表达的变化。接种肿瘤细胞可增加大网膜细胞间粘附分子（ICAM）-1的表达，而PEG-过氧化氢酶可抑制ICAM-1的表达。在肿瘤接种后3天注射PEG-过氧化氢酶也减少了肿瘤细胞的数量，表明除了肿瘤细胞粘附到腹膜器官之外的过程也被抑制。每日剂量的PEG-过氧化氢酶显着延长荷瘤小鼠的生存时间。这些结果表明，腹腔注射PEG-过氧化氢酶通过清除腹腔中的过氧化氢来抑制肿瘤细胞腹膜播散的多个过程。
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.