Selective inhibition of survival signal transduction pathways enhanced radiosensitivity in human esophageal cancer cell lines in vitro

PURPOSE: The purpose of this study was to examine how selective inhibition of the survival signal transduction pathways affects radiosensitivity in human cancer cell lines. MATERIALS AND METHODS: Two human esophageal cancer cell lines, TE-1 (mutant p53) and TE2 (wild-type p53), were used. To inhibit the pathways selectively, 3 specific kinase inhibitors, AG1478 (an inhibitor of EGFR), PD98059 (an inhibitor of MEK) and LY294002 (an inhibitor of PI3K), were combined with radiation. RESULTS: Radiation in combination with these kinase inhibitors potentiated radiation-induced cell killing synergistically. Enhancement ratios were greater in TE-2 than those in TE-1. Radiation in combination with kinase inhibitors increased the expression of the active form of caspase-3 and the PARP cleavage only in TE-2 that has wild-type p53. CONCLUSION: Targeting the key molecules of the survival signal transduction pathway resulted in potentiation of radiation-induced cell killing. The results of this study suggest that the survival signal transduction pathways would be a molecular target in enhancing radiosensitivity