| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
The purpose of this study was to assess whether radiation can activate survival signals and whether inhibitors of survival signal pathways can increase sensitivity to radiation in human esophageal squamous cell cancer cell lines, TE-1 with mutant type p53 and TE-2 with wild type p53.In both cell lines, irradiation with a dose of 5 Gy activated p42/p44 ERK and AKT/PKB soon after irradiation and the activation reached its peak at 1h (p42/p44 ERK) or 3h (AKT/PKB) and returned to almost the same as control at 6 h. p53, p21WAF-1 and Bax protein expressions were increased after irradiation only in TE-2.Genistein, a tyrosine kinase inhibitor, enhanced radiosensitivity in TE- 1 with an enhancement ratio of 3.2 and in TE-2 with that of 2.2.Genistem abolished radiation-induced activation of p42/p44 ERK and AKT/PKB in both cell lines and increased radiation-induced apoptosis significantly in TE-2, but not in TE- 1.AG1478, an EGFR inhibitor, PD98059, a MEK inhibitor, and LY294002, a PI3-kinase inhibitor, also enhanced rradiosensitivity by abolishing radiation-induced activation of p42/p44 ERK and/or AKT/PKB specifically in both cell lines. This study suggested that survival signals, including p42/p44 ERK and AKT/PKB, may be a involved in determining radiosensitivity, and a inhibitor of survival signal pathways would be a potent therapeutic agent that has an enhancing effect on radiation.
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