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In Vitro Effects of Hypoxia-Inducible Factor 1α on the Biological Characteristics of the SiHa Uterine Cervix Cancer Cell Line
  1. Binzhi Tang, MS*,
  2. Yi Qu, PhD*,
  3. Fengyan Zhao, MS*,
  4. Meng Mao, PhD, MD*,
  5. Jun Tang, MS*,
  6. Xihong Li, MS*,
  7. Donna Ferriero, PhD, MD and
  8. Dezhi Mu, PhD, MD*,
  1. *Department of Pediatrics, West China Women and Children's Hospital, Sichuan University, Chengdu, China; and
  2. Department of Neurology, University of California, San Francisco, CA.
  1. Address correspondence and reprint requests to Dezhi Mu, PhD, MD, Division of Neonatology, Department of Pediatrics, West China Women and Children's Hospital, Sichuan University, China, and Department of Neurology, University of California, San Francisco, CA. E-mail: dezhimu{at}yahoo.com or dezhi.mu{at}ucsf.edu.

Abstract

Introduction: Hypoxia-inducible factor 1α (HIF-1α) 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-1α on the biological characteristics of the uterine cervix cancer (UCC) cell line SiHa, such as proliferation, apoptosis, and migration under normoxia and hypoxia.

Methods: Full-length HIF-1α (fL HIF-1α) and dominant-negative HIF-1α (dn HIF-1α) were transfected into UCC SiHa cells. The expression of HIF-1α 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.

Results: The expression of HIF-1α increased in fL HIF-1α but not in dn HIF-1α SiHa cells. Consistently, the expression of HIF-1α target genes such as VEGF, CXCR 4 , and HGTD-P increased in fL HIF-1α-transfected SiHa cells but decreased in dn HIF-1α-transfected SiHa cells. The UCC cells transfected with fL HIF-1α had increased cellular proliferation and migration. However, the inhibition of HIF-1α through dn HIF-1α attenuated cell proliferation and migration under both normoxia and hypoxia.

Conclusions: Hypoxia-inducible factor 1α 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-1α may be a promising strategy for molecular therapy for UCC.

  • Hypoxia inducible factor 1α
  • Uterine cervix cancer cell SiHa
  • Proliferation
  • Apoptosis
  • Migration

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Footnotes

  • B. Tang and Y. Qu equally contributed to this work.

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