title: Bmi-1 confers adaptive radioresistance to KYSE-150R esophageal carcinoma cells.
abstract: Radiotherapy (RT) is a major modality of cancer treatment. However, tumors often acquire radioresistance, which causes RT to fail. The exact mechanisms by which tumor cells subjected to fractionated irradiation (FIR) develop an adaptive radioresistance are largely unknown. Using the radioresistant KYSE-150R esophageal squamous cell carcinoma (ESCC) model, which was derived from KYSE-150 parental cells using FIR, the role of Bmi-1 in mediating the radioadaptive response of ESCC cells to RT was investigated. The results showed that the level of Bmi-1 expression was significantly higher in KYSE-150R cells than in the KYSE-150 parental cells. Bmi-1 depletion sensitized the KYSE-150R cells to RT mainly through the induction of apoptosis, partly through the induction of senescence. A clonogenic cell survival assay showed that Bmi-1 depletion significantly decreased the radiation survival fraction in KYSE-150R cells. Furthermore, Bmi-1 depletion increased the generation of reactive oxygen species (ROS) and the expression of oxidase genes (Lpo, Noxo1 and Alox15) in KYSE-150R cells exposed to irradiation. DNA repair capacities assessed by γ-H2AX foci formation were also impaired in the Bmi-1 down-regulated KYSE-150R cells. These results suggest that Bmi-1 plays an important role in tumor radioadaptive resistance under FIR and may be a potent molecular target for enhancing the efficacy of fractionated RT.
authors: Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors: Guanyu
authors: G
authors: Wang
authors: Luying
authors: L
authors: Liu
authors: Sherven
authors: S
authors: Sharma
authors: Hai
authors: H
authors: Liu
authors: Weifang
authors: W
authors: Yang
authors: Xiaonan
authors: X
authors: Sun
authors: Qinghua
authors: Q
authors: Dong
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D004260:DNA Repair / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000532:radiotherapy*; D055785:Gene Knockdown Techniques; D006801:Humans; D010088:Oxidoreductases / Q000235:genetics; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism*; D011836:Radiation Tolerance / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C069077:BMI1 protein, human; D017382:Reactive Oxygen Species; D010088:Oxidoreductases; D063150:Polycomb Repressive Complex 1