The depletion of interleukin-8 causes cell cycle arrest and increases the efficacy of docetaxel in breast cancer cells

Biochem Biophys Res Commun. 2013 Feb 15;431(3):535-41. doi: 10.1016/j.bbrc.2013.01.022. Epub 2013 Jan 12.

Abstract

IL-8 is a multi-functional pro-inflammatory chemokine, which is highly expressed in cancers, such as ER-negative breast cancer. The present study demonstrates the pervasive role of IL-8 in the malignant progression of ER-negative breast cancer. IL-8 siRNA inhibited proliferation and delayed the G1 to S cell cycle progression in MDA-MB-231 and BT549 cells. IL-8 silencing resulted in the upregulation of the CDK inhibitor p27, the downregulation of cyclin D1, and the reduction of phosphorylated-Akt and NF-κB activities. IL-8 depletion also increased the chemosensitivity to docetaxel. These results indicate a role for IL-8 in promoting tumor cell survival and resistance to docetaxel and highlight the potential therapeutic significance of IL-8 depletion in ER-negative breast cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology*
  • Cell Cycle Checkpoints / drug effects
  • Cell Cycle Checkpoints / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Docetaxel
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Humans
  • Integrin beta3 / genetics
  • Interleukin-8 / genetics
  • Interleukin-8 / physiology*
  • Middle Aged
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Taxoids / therapeutic use*

Substances

  • Antineoplastic Agents
  • Integrin beta3
  • Interleukin-8
  • RNA, Small Interfering
  • Taxoids
  • Docetaxel