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

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-κB 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-κB 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-κB expression and downregulating the adhesive molecules, such as E-selectin and ICAM-1.