berberine radiosensitizes human esophageal cancer cells by downregulating homologous recombination repair protein rad51小檗碱radiosensitizes人食管癌细胞的表达下调rad51同源重组修复蛋白质.pdfVIP

Berberine Radiosensitizes Human Esophageal Cancer Cells by Downregulating Homologous Recombination Repair Protein RAD51 1. 1. 1 1 1 2 1 Qiao Liu , Haiyan Jiang , Zhaojian Liu , Yu Wang , Minnan Zhao , Chunyan Hao , Shuai Feng , 1 1 3 1 1 Haiyang Guo , Bing Xu , Qifeng Yang , Yaoqin Gong *, Changshun Shao * 1 Key Laboratory of Experimental Teratology, Ministry of Education, and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong, China, 2 Department of Pathology, Qilu Hospital of Shandong University, Jinan, Shandong, China, 3 Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China Abstract Background: Esophageal squamous cell carcinomas (ESCC) have poor prognosis. While combined modality of chemotherapy and radiotherapy increases survival, most patients die within five years. Development of agents that confer cancer cell-specific chemo- and radiosensitivity may improve the therapy of ESCC. We here reported the discovery of berberine as a potent radiosensitizing agent on ESCC cells. Principal Findings: Berberine at low concentrations (,15 mM) substantially radiosensitized ESCC cells. X-ray induced DNA double-strand breaks (DSBs) persist longer in ESCC cells pretreated with berberine. Berberine pretreatment led to a significant downregulation of RAD51, a key player in homologous recombination repair, in ESCC cells, but not in non- malignant human cells. Downregulation of RAD51 by RNA interference similarly radiosensitized the