Evaluation of the Effect of Diclofenac Sodium and 5-Fluourasil in a 3D Cholesteatoma Cell Culture Model

Otol Neurotol. 2019 Sep;40(8):1018-1025. doi: 10.1097/MAO.0000000000002297.

Abstract

Introduction: Middle ear cholesteatoma is a benign disease with invasive and destructive clinical behaviors. It increases the rate of both chronic otitis media complications and revision surgeries. The most effective treatment of middle ear cholesteatoma is surgical excision, and there is no medical treatment for this disease. Exploring new medical treatment options may help to create treatment alternatives instead of surgery.

Materials and methods: Required cholesteatoma tissues for cell culture were excised from 4 different participants who underwent surgery in our clinic and agreed to give tissue for the study. Cholesteatoma-derived keratinocytes and fibroblasts were cocultured in temperature-sensitive culture dishes to make a three-dimensional (3D) cholesteatoma model. Then, the effects of 1% and 2% diclofenac sodium on viability and cell proliferation rates were examined using WST-1 and annexin-V tests.

Results: Cell viability and proliferation rates were found to be lower and apoptosis rates were higher in the diclofenac sodium group versus the negative and positive control groups.

Conclusion: In this present study, we described a new 3D cholesteatoma cell culture model developed using cell sheet technology and demonstrated the efficacy of diclofenac sodium on cholesteatoma for the first time in the literature. It may be used in patients with chronic otitis media with cholesteatoma, but further studies investigating ototoxic and neurotoxic effects of this molecule are needed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Apoptosis / drug effects
  • Cell Culture Techniques / methods*
  • Cholesteatoma, Middle Ear*
  • Coculture Techniques
  • Diclofenac / pharmacology*
  • Female
  • Fibroblasts / drug effects
  • Fluorouracil / pharmacology
  • Humans
  • Keratinocytes / drug effects
  • Male
  • Middle Aged
  • Otitis Media / surgery

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Diclofenac
  • Fluorouracil