A nitroimidazole derivative, PR-350, enhances the killing of pancreatic cancer cells exposed to high-dose irradiation under hypoxia.
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.
Mizumoto
Kazuhiro
K
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. mizumoto@mailserver,med.kyushu-u.ac.jp
Qian
Li-Wu
LW
Zhang
Li
L
Nagai
Eishi
E
Kura
Shinobu
S
Tanaka
Masao
M
D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D015687:Cell Hypoxia; D004273:DNA, Neoplasm / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D007093:Imidazoles; D011838:Radiation-Sensitizing Agents; C106738:doranidazole