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Thiazolidinediones abrogate cervical cancer growth

Beverly R Wuertz1, Lindsay Darrah1, Justin Wudel1

  • 1Molecular Oncology Program, Department of Otolaryngology, University of Minnesota, Minneapolis, MN 55455, USA.

Experimental Cell Research
|February 22, 2017
PubMed

Insights

Thiazolidinedione drugs (TZDs) activate PPAR γ, inhibiting cervical cancer cell growth in vitro and in vivo. These findings suggest TZDs as potential treatments for HPV-associated cancers.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Peroxisome proliferator-activated receptor gamma (PPAR γ) is a nuclear receptor implicated in various cellular processes.
  • Thiazolidinedione drugs (TZDs) are known activators of PPAR γ.
  • PPAR γ activation has been linked to potential anti-cancer effects.

Purpose of the Study:

  • To investigate the anti-cancer effects of three TZDs (pioglitazone, rosiglitazone, and ciglitazone) on cervical cancer.
  • To determine the role of PPAR γ activation in TZD-mediated anti-cancer activity.
  • To evaluate TZD efficacy in both in vitro cell lines and an in vivo animal model.

Main Methods:

  • Utilized three HPV-associated cervical cancer cell lines (CaSki, SiHa, HeLa).
  • Administered pioglitazone, rosiglitazone, and ciglitazone to cell lines and a nude mouse xenograft model.
  • Assessed PPAR γ activation using a luciferase reporter gene assay.
  • Measured cellular proliferation, Oil Red O accumulation, and adipsin expression.

Main Results:

  • All three TZDs significantly increased PPAR γ activation in cervical cancer cell lines.
  • TZDs demonstrated a dose-dependent decrease in cellular proliferation in vitro.
  • In vivo studies showed pioglitazone significantly inhibited HeLa tumor growth in nude mice compared to controls.

Conclusions:

  • TZDs effectively slow cervical tumor cell growth by decreasing proliferation and increasing PPAR γ and adipsin levels.
  • These findings highlight TZDs as potential therapeutic agents or adjuncts for HPV-associated cervical cancers.
  • Further research into TZDs for precancerous conditions is warranted.
Keywords:
Cervical cancerHead and neck cancerPPARPioglitazoneThiazolidinedione

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