Radiation-induced SOD2 overexpression sensitizes colorectal cancer to radiation while protecting normal tissue.
Radiation-induced SOD2 overexpression sensitizes colorectal cancer to radiation while protecting normal tissue.
复制标题
辐射诱导的 SOD2 过度表达使结直肠癌对辐射敏感，同时保护正常组织
DOI：
10.18632/oncotarget.13954
复制
发表时间：
2017-01-31
期刊：
影响因子：
--
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Zhang Z;Lang J;Cao Z;Li R;Wang X;Wang W
本研究探讨了在放射激活基因治疗人结直肠癌的过程中，放射诱导超氧化物歧化酶2（SOD 2）过表达是否对肿瘤细胞产生放射增敏作用，同时对正常细胞具有放射保护作用。将9个串联的CArG盒直接连接到CMV基本启动子上，得到嵌合启动子C9 BC，然后构建由C9 BC启动子驱动的含GFP和SOD 2基因的慢病毒载体。将稳定转染的HT-29大肠癌细胞和CCD 841 CoN正常大肠癌细胞照射至6-戈伊剂量，观察细胞增殖和凋亡。用治疗性慢病毒感染BALB/c小鼠中的肿瘤异种移植物和肿瘤周围皮肤组织，随后用6戈伊的总剂量照射。体外实验显示，与未转染的细胞相比，辐射诱导的SOD 2过表达抑制了肿瘤细胞的增殖（61.89% vs.40.17%，P < 0.01），并减少了正常细胞的凋亡（14.8% vs.9.6%，P = 0.02）。在体内观察到类似的效果。因此，通过嵌合C9 BC启动子辐射诱导的SOD 2过表达增加了HT-29人结肠直肠癌细胞的辐射敏感性，同时保护正常CCD 841 CoN结肠直肠细胞免受辐射损伤。
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.