In Vitro Effects of Hypoxia-Inducible Factor 1α on the Biological Characteristics of the SiHa Uterine Cervix Cancer Cell Line

Abstract

Hypoxia-inducible factor 1alpha (HIF-1alpha) regulates the transcription of many genes involved in key aspects of cancer biology. The aim of our study was to explore the effects of HIF-1alpha on the biological characteristics of the uterine cervix cancer (UCC) cell line SiHa, such as proliferation, apoptosis, and migration under normoxia and hypoxia. Full-length HIF-1alpha (fL HIF-1alpha) and dominant-negative HIF-1alpha (dn HIF-1alpha) were transfected into UCC SiHa cells. The expression of HIF-1alpha and its targets such as vascular endothelial growth factor (VEGF), CXC chemokine receptor 4 (CXCR4), and human growth and transformation-dependent protein (HGTD-P) was detected by immunocytochemistry, Western blot, and semiquantitative reverse transcription-polymerase chain reaction. Cell proliferation, apoptosis, and migration were surveyed by methyl thiazolyl tetrazolium assay, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining, and scratching test. The expression of HIF-1alpha increased in fL HIF-1alpha but not in dn HIF-1alpha SiHa cells. Consistently, the expression of HIF-1alpha target genes such as VEGF, CXCR4, and HGTD-P increased in fL HIF-1alpha-transfected SiHa cells but decreased in dn HIF-1alpha-transfected SiHa cells. The UCC cells transfected with fL HIF-1alpha had increased cellular proliferation and migration. However, the inhibition of HIF-1alpha through dn HIF-1alpha attenuated cell proliferation and migration under both normoxia and hypoxia. Hypoxia-inducible factor 1alpha affects the proliferation, apoptosis, and migration of UCC SiHa cells in part by regulating the expression of its target genes such as VEGF, HGTD-P, and CXCR4. Targeting HIF-1alpha may be a promising strategy for molecular therapy for UCC.