Expression of hypoxia-inducible factor-1alpha in liver tumors after transcatheter arterial embolization in an animal model

Abstract

To examine the effect of transcatheter arterial embolization (TAE) of liver tumors on hypoxia-inducible factor-1alpha (HIF-1alpha) expression in the residual viable tumor, a total of 30 New Zealand White rabbits implanted with VX2 liver tumor were divided into 2 groups. TAE-treated group animals (n=15) were subjected to TAE with 150-250 microm polyvinyl alcohol particles. Control group animals (n=15) underwent sham embolization with distilled water. Six hours, 3 days or 7 days after TAE, the animals were sacrificed, and samples of tumor and adjacent normal liver tissue were harvested. Expression of HIF-1alpha protein was examined immunohistochemically. Real-time PCR was performed to examine the HIF-1alpha mRNA levels. Our results showed that HIF-1alpha protein was expressed in the VX2 tumors but not in the adjacent normal liver tissue. The HIF-1alpha-positive tumor cells were located predominantly at the periphery of necrotic tumor regions. The mean levels of HIF-1alpha protein were significantly higher in TAE-treated tumors than those in control tumors (P=0.002). Among the three sacrificing time points, the difference in increase in HIF-1alpha protein was significant between the two groups at the sacrificing time point of 6 h and 3 days after TAE (P=0.020, P=0.031, respectively), whereas no significant increase was noted 7 days after TAE (P=0.502). In contrast, although HIF-1alpha mRNA was expressed in TAE-treated and control VX2 tumors, there existed no significant difference in the HIF-1alpha mRNA level between the two groups (P=0.372). It is concluded that TAE of liver tumors increases the expression of HIF-1alpha at protein level in the residual viable tumor, which could be attributed to hypoxia generated by the procedure.