Radiation-induced SOD2 overexpression sensitizes colorectal cancer to radiation while protecting normal tissue

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// Zhiqiang Zhang 1, * , Jinyi Lang 2, * , Zhi Cao 3 , Rong Li 4 , Xingyong Wang 1 , Weidong Wang 2 1 Department of Critical Care Medicine, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China 2 Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu 610041, China 3 Department of Radiation Oncology, Sichuan Oncology Institute of Guangxi Medical University, Chengdu 610041, China 4 Institute of Combined Injuries, College of Military Preventive Medicine, Third Military Medical University, Chongqing 400038, China * These authors contributed equally to this work Correspondence to: Weidong Wang, email: wangwd_01@163.com Keywords: superoxide dismutase 2, colorectal cancer, early growth response gene-1, promoter, radiation Received: July 02, 2016 Accepted: December 05, 2016 Published: December 15, 2016 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, C 9 BC, 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 C 9 BC 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 C 9 BC promoter increased the radiosensitivity of HT-29 human colorectal cancer cells and concurrently protected normal CCD 841 CoN colorectal cells from radiation damage.