SNAIL gene inhibited by hypoxia-inducible factor 1 (HIF-1) in epithelial ovarian cancer

摘要

The aim of this study was to investigate the relationship between HIF-1 and SNAIL gene expression in the epithelial ovarian cancer (EOC) cell line. EOC cells were treated with hypoxia, hypoxia combined with rapamycin, and control. The expression of HIF-1 and E-cad were assessed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. The gene expression of SNAIL was studied by RT-PCR and real-time PCR. RNA interference technology was used to determine the relationship between HIF-1 and SNAIL. The present study indicated that the HIF-1 protein was expressed and increased in EOC cell line. SNAIL mRNA was found to increase and E-cad expression decreased with the time of hypoxia prolonged. Hypoxia increased invasion abilities of EOC cell line, but compared with cells exposed to hypoxia, the change of invasive ability of cells with rapamycin had no effect. The expression of HIF-1 protein and SNAIL mRNA could be inhibited gradually by rapamycin. siRNA of HIF-1 could suppress the expression of SNAIL while siRNA of SNAIL had no influence on HIF-1 protein expression. HIF-1 may be the upstream of the SNAIL gene in EOC. Our data suggested that HIF-1 might be an upregulator of the SNAIL gene and HIF-1-SNAIL-E-cad pathway may play an important role in EOC invasion and metastasis.