ShRNA-mediated Ku80 Gene Silencing Inhibits Cell Proliferation and Sensitizes to γ-radiation and Mitomycin C-induced Apoptosis in Esophageal Squamous Cell Carcinoma Lines
| Autor: | Fei-Yue Fan, Qing-shan Yang, Lili Qin, Yong Wang, Liqing Du, Li-Li Jia, Jin-Long Gu |
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| Rok vydání: | 2008 |
| Předmět: |
Esophageal Neoplasms
Mitomycin Health Toxicology and Mutagenesis Apoptosis Biology medicine.disease_cause Radiation Tolerance Cell Line Tumor LNCaP medicine Humans Radiology Nuclear Medicine and imaging MTT assay Gene Silencing RNA Small Interfering Ku Autoantigen Cell Proliferation Radiation Cell growth Antigens Nuclear Cell cycle DNA-Binding Proteins Gamma Rays Cell culture Cancer cell Carcinoma Squamous Cell Cancer research Carcinogenesis |
| Zdroj: | Journal of Radiation Research. 49:399-407 |
| ISSN: | 1349-9157 0449-3060 |
| DOI: | 10.1269/jrr.07096 |
| Popis: | To investigate the effects of Ku80 depletion on cell growth and sensitization to gamma-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 gamma-radiation and MMC was determined with colony formation assay and MTT assay. The cell cycle distribution was determined by Flow cytometry. Apoptosis induced by gamma-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 gamma-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. |
| Databáze: | OpenAIRE |
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