A Nitroimidazole Derivative, PR-350, Enhances the Killing of Pancreatic Cancer Cells Exposed to High-dose Irradiation under Hypoxia | Zendy

Kazuhiro Mizumoto | Zendy; Li-Wu Qian | Zendy; Zhang Li | Zendy; Eishi Nagai | Zendy; Shinobu Kura | Zendy; Masao Tanaka | Zendy

Open Access

A Nitroimidazole Derivative, PR-350, Enhances the Killing of Pancreatic Cancer Cells Exposed to High-dose Irradiation under Hypoxia

Author(s) -

Kazuhiro Mizumoto,

Li-Wu Qian,

Zhang Li,

Eishi Nagai,

Shinobu Kura,

Masao Tanaka

Publication year - 2002

Publication title -

journal of radiation research

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.643

H-Index - 60

eISSN - 1349-9157

pISSN - 0449-3060

DOI - 10.1269/jrr.43.43

Subject(s) - pancreatic cancer , propidium iodide , irradiation , flow cytometry , chemistry , cancer cell , cell culture , radiosensitivity , hypoxia (environmental) , cancer research , microbiology and biotechnology , cancer , biology , medicine , programmed cell death , apoptosis , radiation therapy , biochemistry , oxygen , physics , genetics , organic chemistry , nuclear physics

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.

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