Inhibitory CpG sequences reduced ischemia/reperfusion-induced hepatic metastases of liver tumor in a murine model

• Published in: The Journal of surgical research Vol. 178; no. 1; pp. 248 - 254
• Main Authors: Wang, Jin, MD, Liu, Yi, MD, Zhang, Aiqun, PhD, Li, Chonghui, PhD, Dong, Jiahong, MD, PhD, FACS
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2012
• Subjects: Animals; Cell Line, Tumor; Dinucleoside Phosphates - pharmacology; Disease Models, Animal; Down-Regulation - drug effects; E-Selectin - genetics; E-Selectin - metabolism; Hepatectomy; Hepatic replacement area; Inhibitory CpG sequences; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Ischemia/reperfusion; Laparotomy; Liver Neoplasms - drug therapy; Liver Neoplasms - secondary; Liver Neoplasms - surgery; Male; Metastases; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; Reperfusion Injury - drug therapy; Reperfusion Injury - pathology; RNA, Messenger - metabolism; Surgery; Toll-Like Receptor 9 - antagonists & inhibitors; Toll-Like Receptor 9 - metabolism; Inhibitory CpG sequences; Hepatic replacement area; Ischemia/reperfusion; Metastases
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2012.01.057

Abstract Background It is reported that hepatic ischemia/reperfusion (I/R) during hepatectomy accelerates liver tumor growth. Hepatic I/R induces inflammation cytokines, which can accelerate the outgrowth of liver tumor. Inhibitory CpG sequence (iCpG) is an inhibitor of TLR9, which plays an important role in hepatic I/R. The aim of this study was to examine whether iCpG could prevent hepatic I/R-induced metastases of the liver tumor. Materials and methods A murine tumor model that underwent partial hepatic I/R or sham operation was treated with iCpG or control DNA sequence (Ctrl ODN). Tumor growth and metastases were observed on day 14 after surgery; Endothelial leukocyte adhesion molecules such as E-selectin and intracellular adhesion molecule-1 (ICAM-1) protein expression were measured 24 h after reperfusion by Western blotting; E-selectin and ICAM-1 mRNA expression in hepatic tissue was measured 2 h after reperfusion by RT-PCR; NF- κ B activity in hepatic tissue was measured 2 h after reperfusion by electrophoretic gel mobility shift assay. Results The tumor growth in the mice subjected to hepatic I/R was remarkably stimulated when compared with the mice subjected to laparotomy alone. The iCpG had no significant inhibitory effect on tumor growth in sham-operated mice subjected to tumor. However, iCpG could reduce the tumor growth and inhibit the activation of NF- κ B and downregulate the E-selectin and ICAM-1 mRNA and protein in the mice with tumor subjected to I/R. Conclusions ICpG might reduce I/R-induced hepatic metastases of liver tumor cells by inhibiting NF- κ B expression and downregulating the adhesive molecules, such as E-selectin and ICAM-1.