Inhibition of peritoneal metastasis of human gastric cancer cells by dextran sulphate through the reduction in HIF-1α and ITGβ1 expression

Abstract

The aim of the present study was to investigate the effects of dextran sulphate (DS) on HIF-1α and integrin β1 (ITGβ1) expression in human gastric cancer cells, the correlation between HIF-1α and ITGβ1 expression and the influence of DS on the peritoneal metastasis of human gastric cancer cells. In in vitro experiments, BGC-823 cells in the experimental and control groups were administered DS and PBS, respectively, and exposed to hypoxic conditions for different periods. Immunocytochemistry, western blot and RT-PCR analyses were used to evaluate HIF-1α and ITGβ1 expression levels. In in vivo experiments, an animal model was established by injecting BGC-823 cells into nude mice. The experimental and control groups received DS and PBS injections, respectively. The mice were euthanized at different times, and the number of tumor nodules in the celiac implantation was recorded. Immunohistochemistry, RT-PCR and western blot analyses were used to detect HIF-1α and ITGβ1 expression in the tumor nodules of the greater omentum. The in vitro and in vivo results revealed that HIF-1α and ITGβ1 expression levels in the experimental group were significantly lower than those in the control group (P<0.05), and the expression levels of these factors were positively correlated with each other. The number of tumor nodules in the in vivo experiments was notably less in the experimental group than that noted in the control group (P<0.01). In conclusion, DS may act through inhibition of HIF-1α expression, which decreased ITGβ1 expression, consequently reducing tumor metastasis.