TY - JOUR
T1 - The neutrophil elastase inhibitor sivelestat suppresses accelerated gastrointestinal tumor growth via peritonitis after cecal ligation and puncture
AU - Kumagai, Koshi
AU - Saikawa, Yoshiro
AU - Takeuchi, Hiroya
AU - Suda, Koichi
AU - Fukuda, Kazumasa
AU - Nakamura, Rieko
AU - Takahashi, Tsunehiro
AU - Kawakubo, Hirofumi
AU - Wada, Norihito
AU - Miyasho, Taku
AU - Kitagawa, Yuko
PY - 2013/9
Y1 - 2013/9
N2 - Background: We examined whether tumor growth is enhanced by cecal ligation and puncture (CLP) and suppressed by a neutrophil elastase inhibitor, sivelestat. Materials and Methods: C57BL/6 mice were divided in CLP/sivelestat, CLP alone, and control (simple laparotomy) groups. Murine CT26 colon carcinoma cells were injected subcutaneously into the back of each mouse and tumor growth and serum cytokine levels were assessed. Results: Mice subjected to CLP alone exhibited enhanced tumor growth compared to controls with subcutaneously injected CT26 cells (0.64±0.24 g vs. 0.021±0.027 g, p<0.001), while treatment with CLP/sivelestat produced smaller tumors than CLP alone (0.28±0.23 g vs. 0.64±0.24 g, p=0.006). Cytokine assays showed suppressed production of interleukin (IL)-6 and IL-10 in the CLP/sivelestat group, and increased IL-6 and IL-10 in the CLP-alone group. Conclusion: Intraabdominal inflammation induced by CLP enhances the growth of subcutaneously implanted tumors, while perioperative administration of sivelestat suppresses tumor growth by affecting systemic inflammation.
AB - Background: We examined whether tumor growth is enhanced by cecal ligation and puncture (CLP) and suppressed by a neutrophil elastase inhibitor, sivelestat. Materials and Methods: C57BL/6 mice were divided in CLP/sivelestat, CLP alone, and control (simple laparotomy) groups. Murine CT26 colon carcinoma cells were injected subcutaneously into the back of each mouse and tumor growth and serum cytokine levels were assessed. Results: Mice subjected to CLP alone exhibited enhanced tumor growth compared to controls with subcutaneously injected CT26 cells (0.64±0.24 g vs. 0.021±0.027 g, p<0.001), while treatment with CLP/sivelestat produced smaller tumors than CLP alone (0.28±0.23 g vs. 0.64±0.24 g, p=0.006). Cytokine assays showed suppressed production of interleukin (IL)-6 and IL-10 in the CLP/sivelestat group, and increased IL-6 and IL-10 in the CLP-alone group. Conclusion: Intraabdominal inflammation induced by CLP enhances the growth of subcutaneously implanted tumors, while perioperative administration of sivelestat suppresses tumor growth by affecting systemic inflammation.
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M3 - Article
C2 - 24023292
AN - SCOPUS:84885003494
SN - 0250-7005
VL - 33
SP - 3653
EP - 3660
JO - Anticancer research
JF - Anticancer research
IS - 9
ER -
