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Inhibition of surgical trauma-enhanced peritoneal dissemination of tumor cells by human catalase derivatives in mice

2011; Elsevier BV; Volume: 51; Issue: 3 Linguagem: Inglês

10.1016/j.freeradbiomed.2011.05.025

1873-4596

Chika Nishizaki, Makiya Nishikawa, Tomoya Yata, Toshiyuki Yamada, Yuki Takahashi, Masahide Oku, Hiroya Yurimoto, Yasuyoshi Sakai, Kenji Nakanishi, Yoshinobu Takakura,

Cardiac, Anesthesia and Surgical Outcomes

Surgical trauma, which is inevitably associated with the surgical removal of cancer, has been reported to accelerate tumor metastasis.The close association of reactive oxygen species with the trauma and tumor metastasis supports the possibility of using antioxidants for the inhibition of metastasis.To inhibit surgical trauma-enhanced peritoneal dissemination, human catalase (hCAT) derivatives, i.e., hCAT-nona-arginine peptide (hCAT-R9) and hCAT-albumin binding peptide (hCAT-ABP), were designed to increase the retention time of the antioxidant enzyme in the abdominal cavity after intraperitoneal administration.Both 125 I-labeled ( 125 I-) derivatives showed significantly prolonged retention in the cavity than 125 I-hCAT.Cauterization of the cecum of mice with a hot iron, an experimental model of surgical trauma, induced abdominal adhesions.In addition, cauterization followed by colon26 tumor cell inoculation increased lipid peroxidation in the cecum and mRNA expression of molecules associated with tissue repair/adhesion and inflammation in the peritoneum.hCAT derivatives significantly suppressed the increased mRNA expression.The cauterization also increased the number of tumor cells in the abdominal organs, and the number was significantly reduced by hCAT-R9 or hCAT-ABP.These results indicate that hCAT-R9 and hCAT-ABP, both of which have a long retention time in the peritoneal cavity, can be effective in inhibiting surgery-induced peritoneal -3 -metastasis.