摘要
目的:研究西妥昔单抗(Cetuximab,C225)对耐多西他赛(Docetaxel)肺腺癌细胞株SPC-A-1/docetaxel放化疗敏感性的调变作用。方法:克隆形成实验观察C225对SPC-A-1/docetaxel细胞株放疗敏感性的影响;MTT比色法观察C225单独应用以及不同次序联合多西他赛对SPC-A-1/docetaxel细胞株的生长抑制作用;流式细胞术检测C225对SPC-A-1/docetaxel细胞凋亡及细胞生长周期的影响。结果:C225联合放疗可以显著减少SPC-A-1/docetaxel细胞的克隆形成数目,其D_0值以及单纯放疗的D_0值分别为1.73 Gy和2.39 Gy,增敏比为1.38。C225单药即使在高达1 000μg/ml的质量浓度下作用48 h对SPC-A-1/docetaxel细胞无细胞毒和生长抑制作用;在使用多西他赛之后使用C225,多西他赛的IC_(50)值为85.2μg/ml,较单独使用多西他赛时的IC_(50)值128.7μg/ml显著降低。C225单独应用可以诱导SPC-A-1/docetaxel细胞凋亡,并具有时间效应。C225处理(24h)前后G_1期细胞比例分别为(43.80±4.46)%及(60.50±6.57)%(P<0.05)。结论:C225增加了SPC-A-1/do- cetaxel细胞株对放化疗的敏感性,其机制可能与其诱导凋亡及G_1期细胞周期阻滞有关。
Objective： To investigate the modulating effects of anti-epidermal growth factor monoclonal antibody Cetuximab（ C225 ） on the chemosensitivity and radiosensitivity in a Docetaxel-resistant human lung adenocarcinoma cell line SPC-A-1/docetaxel. Methods： Radiosensitivity of SPC-A-1/docetaxel was determined by clone formation experiment and quantified by calculating the enhancement ratio （ER）. The growth inhibition of SPC-A-1/docetaxel cell line caused by C225 or combination of C225 and Docetaxel in different orders was detected by MTT assay. The effect of C225 on cell cycle distribution and apoptosis was determined by flow cytometry. Results： C225 combined with radiation significantly decreased the number of the cell clones than radiation alone ; the Do values were 1.73 Gy for the former and 2.39 Gy for the latter, and the enhancement ratio was 1.38. C225 alone at concentration up to 1 000 μg/ml for 48 h had neither cytotoxic nor cytostatic effect on SPC-A-1/docetaxel in vitro. C225 administration followed by Docetaxel significantly decreased the IC50 of Docetaxel （85.2 μg/ml vs 128.7 μg/ml）. Flow cytometry demonstrated that C225 exposure induced apoptosis of SPC-A-1/docetaxel cells in a time-dependent manner. The cell in the G0/G1 fraction increased from （43.80 ± 4.46 ）% to （ 60.50 ± 6.57 ） % （ P 〈 0.05 ） after a 24 h C225 exposure. Conclusion： C225 can enhance the radiosensitivity and chemosensitivity of the Docetaxel-resistant lung adenocarcinoma cell line SPC-A-1/docetacel, which may be associated with apoptosis induction and cell cycle arrest at G1 phase.
出处
《中国肿瘤生物治疗杂志》
CAS
CSCD
2007年第5期450-454,共5页
Chinese Journal of Cancer Biotherapy
基金
江苏省博士后科研资助基金(No.0602031B)
Supported by Postdoctoral Research Foundation of Jiangsu Province(No.0602031B)
关键词
表皮生长因子受体
西妥昔单抗
放疗
化疗
敏感性
肺癌
epidemal growth factor receptor
Cetuximab （C225）
chemosensitivity
radiosensitivity
lung cancer
