Publications (2)0 Total impact
Article: [Effect and mechanism of gefitinib inhibition on non-small cell lung cancer radiosensitivity of HCC827 and H358 cell lines].[show abstract] [hide abstract]
ABSTRACT: The epidermal growth factor receptor (EGFR) 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 cell lines. The study also aims to elucidate the mechanism, by which this drug restores the radiosensitivity of NSCLC cells. 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 μmol/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 γ-H2AX repair and EGFR foci after irradiation. Nuclear EGFR expression was also detected by Western blot analysis after radiotherapy. 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 H358 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. 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.Zhongguo fei ai za zhi = Chinese journal of lung cancer 06/2012; 15(6):324-31.
Article: [Effection and mechanism of radiosensitivity of non-small cell lung cancer cell line H358 following gefitinib treatment].[show abstract] [hide abstract]
ABSTRACT: The epidermal growth factor receptor (EGFR) is an important determinant of radioresponse, the elevated expression and activity of which frequently correlates with radioresistance in several cancers, including non-small-cell lung carcinoma (NSCLC). The molecular blockade of EGFR signaling is a promising therapeutic strategy for the enhancement of the cytotoxic effects of radiotherapy. The aims of the present study are to observe whether gefitinib, a selective EGFR tyrosine kinase inhibitor, can radiosensitize the NSCLC H358 cell line and to investigate the mechanism by which this drug restores the radiosensitivity of NSCLC cells. NSCLC cell line H358 was divided into two groups, namely the X-ray and the gefitinib-interfering groups. The former was irradiated using X-ray only, and the latter was treated with 1 μmol/L gefitinib 24 h before irradiation under the same conditions. The cells were tested using the clonogenic cell survival assay to identify the radiosensitivity of both groups. Immunostaining for confocal microscopy was used to observe nuclear γ-H2AX repair and EGFR foci after irradiation. Nuclear EGFR expression was detected using Western blot after radiotherapy. In the clonogenic cell survival assay, the survival fraction in the gefitinib-interfering group was lower than that in the X-ray group at different doses. Surviving fraction of 2 Gy (SF2) were 0.000,865 and 0.011,1 for the gefitinib-interfering and the X-ray groups, respectively. Sensivive enhancement ratio (SER) was 2.815. Immunostaining for confocal microscopy suggested that more nuclear γ-H2AX foci are present in the gefitinib-interfering group than in the X-ray group. The nuclear γ-H2AX foci also stayed longer in the gefitinib-interfering group. EGFR translocated into the nucleus within 1 h in X-ray group, but stayed in the cytoplasma in the gefitinib-interfering group. Western blot was tested using SPSS 13.0, P=0.042. Gefitinib, at the cellular level, radiosensitizes EGFR with NSCLC H358 by blocking EGFR nuclear translocation as one of its mechanisms.Zhongguo fei ai za zhi = Chinese journal of lung cancer 11/2011; 14(11):841-7.