A nitroimidazole derivative, PR-350, enhances the killing of pancreatic cancer cells exposed to high-dose irradiation under hypoxia

J Radiat Res. 2002 Mar;43(1):43-51. doi: 10.1269/jrr.43.43.

Abstract

The radiosensitizing effects of PR-350, a nitroimidazole derivative, were examined concerning the cell killing of human pancreatic cancer cell lines exposed to high doses of gamma-ray irradiation in vitro. The percentages of dead cells were analyzed with a multiwell plate reader to measure the fluorescence intensity of propidium iodide before and after a digitonin treatment. The sensitizing effect of PR-350 on cell killing by high-dose irradiation was confirmed by time-course, dose-dependency, and microscopic observations. In five of seven pancreatic cancer cell lines in which the number of dead cells was determined 5 days after 30 Gy irradiation in the presence of PR-350, the number was significantly increased under hypoxic conditions, but not under aerobic conditions. The selective radiosensitive effect of PR-350 on hypoxic cells was also confirmed by flow cytometry. The results indicate that PR-350 can enhance the killing of pancreatic cancer cells by high-dose irradiation under hypoxia, which supports its clinical radiosensitizing effects when administered during intraoperative irradiation to pancreatic cancer.

MeSH terms

  • Cell Death / drug effects
  • Cell Death / radiation effects
  • Cell Hypoxia
  • DNA, Neoplasm / drug effects
  • DNA, Neoplasm / radiation effects
  • Humans
  • Imidazoles / pharmacology*
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / radiotherapy*
  • Radiation Tolerance
  • Radiation-Sensitizing Agents / pharmacology*
  • Tumor Cells, Cultured

Substances

  • DNA, Neoplasm
  • Imidazoles
  • Radiation-Sensitizing Agents
  • doranidazole