Downregulation of HOTAIR Expression Mediated Anti-Metastatic Effect of Artesunate on Cervical Cancer by Inhibiting COX-2 Expression

PLoS One. 2016 Oct 13;11(10):e0164838. doi: 10.1371/journal.pone.0164838. eCollection 2016.

Abstract

Artesunate (ART) has anti-cancer activities for a variety of solid tumors. The aim of this study was to investigate the anti-metastatic effect of ART on cervical cancer cells. In vivo anti-metastatic effect of ART was investigated in mice with the lung metastasis model by the subcutaneous injection of ART. The interaction of HOTAIR and COX-2 was measured by RNA immunoprecipitation and RNA pull-down assay. The effect of ART on metastasis of CaSki and Hela cells was evaluated by invasion and migration assay. We found that ART inhibited cervical cancer metastasis and HOTAIR expression. HOTAIR overexpression partially abolished the anti-metastatic effect of ART on cervical cancer cells. In addition, HOTAIR can interact with COX-2 to positively regulate COX-2 expression and catalytic activity. Finally, overexpression of COX-2 reversed the effect of HOTAIR knockdown on Hela cell migration and invasion. Taken together, our data revealed that ART may elicit anti-metastatic effect against cervical cancer by inhibition of HOTAIR expression, which resulted in the decrease of COX-2 expression.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Agents / toxicity*
  • Artemisinins / chemistry
  • Artemisinins / therapeutic use
  • Artemisinins / toxicity*
  • Artesunate
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cyclooxygenase 2 / chemistry
  • Cyclooxygenase 2 / metabolism*
  • Dinoprostone / metabolism
  • Down-Regulation / drug effects*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Lung Neoplasms / prevention & control
  • Lung Neoplasms / secondary
  • Mice
  • Mice, Nude
  • Protein Binding
  • RNA Interference
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / metabolism
  • Transplantation, Heterologous
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Artemisinins
  • HOTAIR long untranslated RNA, human
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Artesunate
  • Cyclooxygenase 2
  • Dinoprostone

Grants and funding

The authors received no specific funding for this work.