Hypoxia promotes the proliferation of cervical carcinoma cells through stimulating the secretion of IL-8

Int J Clin Exp Pathol. 2014 Jan 15;7(2):575-83. eCollection 2014.

Abstract

To explore whether hypoxia and interleukin 8 (IL-8) regulate the viability and apoptosis of cervical carcinomas cells and the possible mechanism. We evaluated the expression of hypoxia inducible factor-1α (HIF-1α), IL-8 and its receptors (CXCR1 and CXCR2) in cervical cancer and cervicitis tissues by immunohistochemistry. Then the effects of hypoxia and IL-8 on the viability and apoptosis of HeLa and SiHa cells were detected by the SRB and apoptosis assays. Here we observed that the expression of HIF-1α, IL-8 and CXCR1 in cervical cancer tissues was significantly higher than that in cervicitis tissues. Hypoxic condition stimulated the secretion of IL-8 and the expression of CXCR1 and CXCR2 on HeLa and SiHa cells. Recombinant human IL-8 enhanced the viability and reduced the apoptosis in HeLa and SiHa cells. HeLa and SiHa cells cultured in 1% oxygen showed the increased viability and apoptosis, and the former effect could be partly reversed by anti-human IL-8 neutralizing antibody. This data suggested that IL-8 secreted by cervical carcinomas cells induced by hypoxia can stimulate the viability of cervical carcinomas cells in an autocrine dependent manner, and contribute to the pathogenesis of cervical cancer.

Keywords: Hypoxia; IL-8; apoptosis; cervical carcer cells; viabilty.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / pharmacology
  • Apoptosis
  • Autocrine Communication
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Hypoxia
  • Cell Proliferation* / drug effects
  • Cell Survival
  • Female
  • HeLa Cells
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Interleukin-8 / antagonists & inhibitors
  • Interleukin-8 / immunology
  • Interleukin-8 / metabolism*
  • Receptors, Interleukin-8A / metabolism
  • Receptors, Interleukin-8B / metabolism
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • Up-Regulation
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervicitis / immunology
  • Uterine Cervicitis / metabolism
  • Uterine Cervicitis / pathology

Substances

  • Antibodies, Neutralizing
  • CXCL8 protein, human
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Interleukin-8
  • Receptors, Interleukin-8A
  • Receptors, Interleukin-8B
  • Recombinant Proteins