Melittin radiosensitizes esophageal squamous cell carcinoma with induction of apoptosis in vitro and in vivo

Tumour Biol. 2014 Sep;35(9):8699-705. doi: 10.1007/s13277-014-2146-z. Epub 2014 May 29.

Abstract

Currently, unresectable esophageal squamous cell carcinoma (ESCC) is primarily treated by chemoradiotherapy. However, the outcome has not improved significantly because of radioresistance of cancer cells. This study aimed to determine the radiosensitizing effect of melittin, a novel component of bee venom, in ESCC. ESCC cell lines were irradiated with or without melittin. Cell proliferation was detected by Cell Counting Kit 8 assay. Radiosensitization was evaluated by clonogenic survival assay. Cell apoptosis was detected by flow cytometry. Results show that melittin potently sensitized ESCC cells to radiation with a sensitization enhancement ratio of 1.15-1.42. Radiosensitization was accompanied with enhanced apoptosis and regulated by apoptosis proteins. The results were confirmed by in vivo studies on tumor-bearing xenografts. In summary, these results provide support that melittin may be a potentially promising radiosensitizer in ESCC radiation therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / radiation effects*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Chemoradiotherapy / methods
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / therapy*
  • Flow Cytometry
  • Humans
  • Immunoblotting
  • Male
  • Melitten / pharmacology*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microscopy, Confocal
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Radiation-Sensitizing Agents / pharmacology
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / metabolism

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • Radiation-Sensitizing Agents
  • bcl-2-Associated X Protein
  • Melitten