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  • 标题:ShRNA-mediated Ku80 Gene Silencing Inhibits Cell Proliferation and Sensitizes to γ-radiation and Mitomycin C-induced Apoptosis in Esophageal Squamous Cell Carcinoma Lines
  • 其他标题:ShRNA-mediated Ku80 Gene Silencing Inhibits Cell Proliferation and Sensitizes to γ-radiation and Mitomycin C-induced Apoptosis in Esophageal Squamous Cell Carcinoma Lines
  • 本地全文:下载
  • 作者:Qing-Shan YANG ; Jin-Long GU ; Li-Qing DU
  • 期刊名称:Journal of Radiation Research
  • 印刷版ISSN:0449-3060
  • 电子版ISSN:1349-9157
  • 出版年度:2008
  • 卷号:49
  • 期号:4
  • 页码:399-407
  • DOI:10.1269/jrr.07096
  • 摘要:To investigate the effects of Ku80 depletion on cell growth and sensitization to γ-radiation and MMC-induced apoptosis in esophageal squamous cell carcinoma lines. Six human carcinoma cell lines (LNcaP, K562, MDA-MB-231, MCF-7, EC9706, and K150) and normal HEK293 cell line were examined for basal levels of Ku80 protein by western blotting analysis. The suppression of Ku80 expression was performed using vector-based shRNA in EC9706 cells. Cell proliferation was determined with MTT assay and colony formation assay and tumorigenicity in a xenograft model in vitro and in vivo. Sensitivity of EC9706 cells treated with shRNA vector to γ-radiation and MMC was determined with colony formation assay and MTT assay. The cell cycle distribution was determined by Flow cytometry. Apoptosis induced by γ-radiation and MMC was analyzed using GENMED-TUNEL FACS kit. Ku80 showed higher basal levels in six carcinoma cell lines than in HEK293. The suppression of Ku80 expression decreased cellular proliferation, colony formation and inhibited tumorigenicity in a xenograft model. Furthermore, it sensitized apoptosis of the cancer cells induced by γ-radiation and MMC. Ku80 plays an important role not only in tumorigenesis but also in radiation resistance and chemotherapy resistance in esophageal cancer cells. Hence Ku80 may serve as a promising therapeutic target, particularly for recurrent esophageal tumors.
  • 关键词:Ku80; shRNA; Proliferation; Apoptosis; Esophageal cancer
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