中国肺癌杂志2012，Vol.15Issue(6)：324-331,8.DOI:10.3779/j.issn.1009-3419.2012.06.02
吉非替尼对肺癌细胞株HCC827和H358放射敏感性的影响及其机制研究
Effect and Mechanism of Gefitinib Inhibition on Non-small Cell Lung Cancer Radiosensitivity of HCC827 and H358 Cell Lines
摘要
Abstract
Background and objective The epidermal growth factor receptor (F.GFR) is an important determinant of tumor response to ionizing radiation. Elevated levels of EGFR expression and activity are frequently correlated with the radiotherapy resistance of tumors, including that of non-small cell lung cancer (NSCLC). The molecular inhibition of EGFR signaling is a promising therapeutic strategy for enhancing the cytotoxic effects of radiotherapy. The aim of the present study is to determine whether gefitinib, a selective EGFR tyrosine kinase inhibitor, can radiosensitize the NSCLC H358 and HCC827 tell lines. The study also aims to elucidate the mechanism, by which this drug restores the radiosensitivity of NSCLC cells. Methods The two cell lines were divided into two groups, the X-ray and gefitinib-interfering groups. The former was irradiated with X-rays only, and the latter was treated with 1 祄ol/L gefitinib for 24 h before irradiation under the same conditions as those for the first group. Clonogenic cell survival assay was performed to determine the radiosensitivity of both cell groups. Immunostaining for confocal microscopy was performed to observe nuclear y-H2AX repair and EGFR foci after irradiation. Nuclear EGFR expression was also detected by Western blot analysis after radiotherapy. Results The clonogenic cell survival assay revealed that the surviving fraction at 2 Gy (SF2) of the gefitinib-interfering group (0.355) was lower than that of the X-ray group (0.433) in H358 cells. There was no significant difference between the SF2 values of the two respective groups in HCC827 cells (0.223 vs 0.242). The confocal microscopy results found that gefitinib increased the average number of γ-H2AX foci after irradiation in H3S8 cells, but did not affect the foci in HCC827 cells. Based on confocal microscopy and Western blot analyses, gefitinib also inhibited the translocation of EFGR into the nuclei of H358 cells. However, EGFR was not observed in the nuclei of HCC827 cells for both treatment groups. Conclusion Gefitinib enhances the radioresponse of H358 cells, which may be attributed to the suppression of EGFR transport into the nucleus. However, gefitinib does not affect HCC827 cells, where EGFR remains in the cytoplasm after irradiation.关键词
表皮生长因子受体/肺肿瘤/辐射耐受性/吉非替尼Key words
Epidermal growth factor receptor/ Lung neoplasms/ Radiation tolerance/ Gefitinib分类
医药卫生引用本文复制引用
高子夜,庄亮,陈元..吉非替尼对肺癌细胞株HCC827和H358放射敏感性的影响及其机制研究[J].中国肺癌杂志,2012,15(6):324-331,8.基金项目
本研究受吴阶平医学基金会基金(No.320.6720.10013)和国家自然科学基金(No.30801351)资助 （No.320.6720.10013）
