Abstract:

Objective  To study the relationship between epidermal growth factor receptor （EGFR）， transforming growth factor-α（TGF-α） and different fractional doses of radiotherapy in lung cancer cells and its possible mechanism. Methods Lung cancer cell line A549 cells were irradiated with conventional fractionation （2Gy／day） and large fractionation （4，8 Gy／day）， DT=8 Gy. Real-time fluorescence quantitative PCR （QPCR）， enzyme-linked immunosorbent assay （ELISA） and Western blotting were used to detect EGFR， TGF-α gene and protein expression in A549 cells， respectively. In addition， the expression of γ-H2AX was determined by immunofluorescence assay. Results The expression levels of EGFR mRNA and TGF-α mRNA in A549 cells of 4 Gy／day and 8 Gy／day fractionation groups were significantly lower than those of 2 Gy／day fractionation group （P＜0.05）. The expressions of EGFR and TGF-α proteins in A549 cells of 4 Gy／day and 8 Gy／day fractionation groups were significantly lower than those of 2 Gy／day fractionation group （P＜0.05）. Immunofluorescence assay showed that the expression ofγ-H2AX in A549 cells in 4 Gy／day and 8 Gy／day fractionation groups was significantly higher than that in control group and 2 Gy／day fractionation group. Conclusion The expression of EGFR and TGF-α decreased significantly after high dose fractionated radiotherapy， which increased the sensitivity of A549 cells to radiation. The mechanism may be related to the up-regulation of the expression of histone γ-H2AX in DNA damage repair.

Key words: Lung cancer, Radiotherapy, EGFR, TGF-α