title: Radiation-induced SOD2 overexpression sensitizes colorectal cancer to radiation while protecting normal tissue.
abstract: This study investigated whether radiation-induced overexpression of superoxide dismutase 2 (SOD2) exerts radio-sensitizing effects on tumor cells while having radio-protective effects on normal cells during radio-activated gene therapy for human colorectal cancer. A chimeric promoter, C9BC, was generated by directly linking nine tandem CArG boxes to a CMV basic promoter, after which lentiviral vectors containing GFP and SOD2 gene driven by the C9BC promoter were constructed. Stably transfected HT-29 colorectal cancer cells and CCD 841 CoN normal colorectal cells were irradiated to a dose of 6-Gy, and cell proliferation and apoptosis were observed. Tumor xenografts and peritumoral skin tissue in BALB/c mice were infected with the therapeutic lentivirus and subsequently irradiated with a total dose of 6 Gy. In vitro experiments revealed that radiation-induced SOD2 overexpression inhibited tumor cell proliferation (61.89% vs. 40.17%, P < 0.01) and decreased apoptosis among normal cells (14.8% vs. 9.6%, P = 0.02) as compared to untransfected cells. Similar effects were observed in vivo. Thus radiation-induced SOD2 overexpression via the chimeric C9BC promoter increased the radiosensitivity of HT-29 human colorectal cancer cells and concurrently protected normal CCD 841 CoN colorectal cells from radiation damage.
authors.affiliation: Department of Critical Care Medicine, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu 610041, China.
authors.forename: Jinyi
authors.initials: J
authors.lastname: Lang
authors.affiliation: Department of Radiation Oncology, Sichuan Oncology Institute of Guangxi Medical University, Chengdu 610041, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Institute of Combined Injuries, College of Military Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Critical Care Medicine, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
authors.forename: Xingyong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu 610041, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy*; D004307:Dose-Response Relationship, Radiation; D004790:Enzyme Induction; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D019073:HT29 Cells; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011401:Promoter Regions, Genetic; D011832:Radiation Injuries / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics; D013997:Time Factors; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D000099156:Superoxide Dismutase 2
chemical_list: D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2
keywords: colorectal cancer; early growth response gene-1; promoter; radiation; superoxide dismutase 2