Peroxisome proliferator-activated receptor gamma (PPAR γ) is activated by thiazolidinedione drugs (TZDs) and can promote anti-cancer properties. We used three TZDs (pioglitazone, rosiglitazone, and ciglitazone) to target cervical cancer cell lines and a nude mouse animal model. Each agent increased activation of PPAR γ, as judged by a luciferase reporter gene assay in three HPV-associated cell lines (CaSki, SiHa, and HeLa cells) while decreasing cellular proliferation in a dose-dependent manner. They also promoted Oil Red O accumulation in treated cell lines and upregulated the lipid differentiation marker adipsin. Interestingly, xenograft HeLa tumors in nude mice treated with 100 mg/kg/day pioglitazone exhibited decreased growth compared to control mice or mice treated with standard cervical chemotherapy. In conclusion, TZDs slow tumor cell growth in vitro and in vivo with decreases in cell proliferation and increases in PPAR γ and adipsin. These agents may be interesting treatments or treatment adjuncts for HPV-associated cancers or perhaps even precancerous conditions.
Bibliographical noteFunding Information:
This work was supported by the National Organization for Rare Disorders (NORD) http://www.rarediseases.org/(FGO), Lion's 5M Minnesota (FGO), and NCI/NIH P30 CA77598-07 (FGO). We thank Drs. Abby Meyer and Daniel Schneider for their critical review of the manuscript.
Copyright 2017 Elsevier B.V., All rights reserved.
- Cervical cancer
- Head and neck cancer