Over-expression of PDE5 in Oral Squamous Cell Carcinoma - Effect of Sildenafil Citrate

Anticancer Res. 2021 May;41(5):2297-2306. doi: 10.21873/anticanres.15005.

Abstract

Background/aim: Phosphodiesterase 5 (PDE5) holds clinical relevance in several pathological states, including lung, breast, and prostate cancer. In this study, we examined PDE5 expression in oral squamous cell carcinoma (OSCC)-derived cell lines and tissues, and the anti-tumour effect of PDE5 inhibitor, sildenafil citrate (SC).

Materials and methods: Cell proliferation, cell invasion, and gap closure assays were performed in six OSCC-derived cell lines upon treatment with varying concentrations of SC. PDE5 expression was determined in primary OSCC tissues by western blotting and immunohistochemistry.

Results: Elevated PDE5 expression was observed in all cell lines. A concentration-dependent decrease in cell viability, invasion rate, and migration was observed after SC treatment. A significant correlation (p=0.05) was observed between elevated PDE5 expression and lymphatic infiltration in OSCC tissues.

Conclusion: PDE5 plays an important role in carcinogenesis of OSCC, and the specific inhibition of PDE5 may be an effective chemotherapeutic strategy.

Keywords: PDE5 inhibitor; Phosphodiesterase 5; oral squamous cell carcinoma; sildenafil citrate.

MeSH terms

  • Blotting, Western
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cyclic Nucleotide Phosphodiesterases, Type 5 / metabolism*
  • Dose-Response Relationship, Drug
  • Humans
  • Immunohistochemistry
  • Mouth Neoplasms / enzymology*
  • Mouth Neoplasms / pathology
  • Phosphodiesterase 5 Inhibitors / pharmacology
  • Sildenafil Citrate / pharmacology*

Substances

  • Phosphodiesterase 5 Inhibitors
  • Sildenafil Citrate
  • Cyclic Nucleotide Phosphodiesterases, Type 5