Longer warm ischemia can accelerate tumor growth through the induction of HIF-1α and the IL-6-JAK-STAT3 signaling pathway in a rat hepatocellular carcinoma model.

BACKGROUND

The present study aimed to investigate the impact of the duration of hepatic pedicle clamping (HPC) on tumor growth after major hepatectomy in a rat model.

METHODS

Rats were divided into four groups according to the length of HPC during 70% partial hepatectomy followed by N1S1 tumor cell implantation: group 1, without HPC; group 2, with 5-min HPC; group 3, 10-min HPC; and group 4, 15-min HPC. At three weeks after tumor cell implantation, liver tumor growth and its possible mechanisms were investigated.

RESULTS

The number and largest diameter of liver tumor were significantly greater in group 4. At 6 h after reperfusion, serum levels of inflammatory cytokines including interleukin (IL)-6 were significantly higher in group 4 compared with the other groups. In the tumor tissues, the expression of hypoxia inducible factor (HIF)-1α (P < 0.001 versus group 2, P < 0.001 versus group 3) and that of phospho-signal transducer and activator of transcription 3 (STAT3) (P < 0.001 versus group 2, P = 0.026 versus group 3) were significantly upregulated in group 4.

CONCLUSIONS

Longer HPC followed by reperfusion accelerated hepatocellular carcinoma growth through the induction of HIF-1α and the activation of the IL-6-JAK-STAT3 signaling pathway.