• Binzhi Tang, Yi Qu, Fengyan Zhao, Meng Mao, Jun Tang, Xihong Li, Donna Ferriero, and Dezhi Mu.
• Department of Pediatrics, West China Women and Children's Hospital, Sichuan University, Chengdu, China.
• Int. J. Gynecol. Cancer. 2009 Jul 1; 19 (5): 898-904.

IntroductionHypoxia-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.MethodsFull-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.ResultsThe 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.ConclusionsHypoxia-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.

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