| Budget Amount *help |
¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Research Abstract |
The aim of this study was to evaluate whether radiation induces migration in human non-small cell lung cancer(NSCLC) cells with and without an EGFR mutation(A549 ; wild type, HCC827 ; mutant type). A further aim was to investigate the effects ofradiation induced cell migration by the cells after blocking the EGFR and its downstream pathways by gefitinibin vitro. Cell migrationof A549 cells and HCC827cellswas assessed using a wound healing assay. Cell growth and apoptosis were measured by the WST-1 assay and TUNEL assay, respectively. Cell cycle perturbation and EGFR signal transduction were analyzed by flow-cytometry and Western blotting. The migration distance of the HCC827 cells was significantly decreased bygefitinib and/or irradiation, and the death of the cells HCC827 cells wasincreased with gefitinib and/or irradiation after 48hours or more in comparison to untreated the cells. There was no difference inthe behavior of A549 cells with the treatment.
TheWST-1 assay showed that the
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HCC827 cells were sensitive to increasing concentrationsof gefitinib for 72 hours or more. A variation in the apoptotic pathway was revealed by Western blotting using specific antibodies with cleaved PARP irradiated 2hours after with or without gefitinib. The activation of the apoptosis pathway was confirmed by increased cleaved PARP in HCC827 cells treated with gefitinib.
G2/M phase arrest and increased subG1 in cell cycle was seen in the combination gefitinib and irradiation treatment group of HCC827 cells. The gefitinib and/or irradiation combination treatment could inhibit the phosphorylated ratio of ERK by down-regulating the expression of ERK 1/2 proteins in HCC827 cells. No apoptosis was detected by the TUNEL method in the time course of 24h, 48h, or 72h. Consequently, gefitinib reduced the early migration adhesion ability, and early apoptosis in cells with a genetic mutation of EGFR. Gefitinibshowed a cytotoxic effect and inhibited cell migration in HCC827 cells. The tyrosine kinase receptor inhibitor, gefitinibcombined with radiotherapy may be cytotoxic to NSCLC cells with a genetic mutation of EGFR with subsequent inhibition of their cellular behavior, including proliferation, invasiveness, and metastatic activity. The tyrosine kinase receptor inhibitor-targeted combined radiotherapy regimen may provide a new treatment forthe prevention of early invasion and metastasis for advanced lung cancer. Less
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