The effects of 5-fluorouracil alone and in combination with 13-cis retinoic acid and vitamin D3 on human oral squamous cell carcinoma lines

J Contemp Dent Pract. 2012 May 1;13(3):345-50. doi: 10.5005/jp-journals-10024-1149.

Abstract

Aim: Oral squamous cell carcinoma (OSCC) is responsible for about 90% of oral malignancies and its incidence is increasing. Despite various treatment protocols, survival rate of OSCC is low. Chemotherapy that is used for treating this carcinoma in advanced stages is systemic therapy that destroys carcinogenic cells, and controls tumor metastasis. Chemotherapy is very toxic and has limitations, especially for patients in advanced stages. Considering positive effects of retinoid and vitamin D3 derivatives in treating some carcinomas, we decided to evaluate the effect of combination of these drugs on OSCC. In this study the effects of combination of 5-fluorouracil, 13-cis retinoic acid and vitamin D3 on cultured cell of OSCC have been evaluated.

Materials and methods: OSCC cells were cultured in culture media and different concentration of 5-fluorouracil, 13-cis retinoic acid and vitamin D3 were added to cultured cell as separately and in combinations. The effect of treatment on cell proliferation and induction of apoptosis were evaluated by MTT and TUNEL assays respectively.

Results: Combination of 5-fluorouracil and 13- cis retinoic acid had the highest inhibitory effect on SCC cell proliferation. Combination of two drugs had more apoptotic effect than each of them separately, and combination of three drugs had more effect than combination of two drugs.

Conclusion: Because combination of drugs had more inhibitory effect on cell proliferation than one of them and combination of three drugs had the most apoptotic effect than one of these drugs separately, these drugs may have synergic effect on OSCC.

Clinical significance: Combination of three drugs has more inhibitory effect on cell proliferation and apoptotic effect than one of these drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Carcinoma, Squamous Cell / drug therapy*
  • Cell Line, Tumor / drug effects*
  • Cell Proliferation / drug effects
  • Cholecalciferol / pharmacology*
  • Cholecalciferol / therapeutic use
  • Drug Combinations
  • Drug Synergism
  • Fluorouracil / pharmacology*
  • Fluorouracil / therapeutic use
  • Humans
  • In Situ Nick-End Labeling
  • Isotretinoin / pharmacology*
  • Isotretinoin / therapeutic use
  • Mouth Neoplasms / drug therapy*
  • Tetrazolium Salts
  • Thiazoles

Substances

  • Drug Combinations
  • Tetrazolium Salts
  • Thiazoles
  • Cholecalciferol
  • Isotretinoin
  • thiazolyl blue
  • Fluorouracil