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.

Redox Paradox: A Novel Approach to Therapeutics-Resistant Cancer

“…This study was the first to suggest that increasing MnSOD activity could be a tool to enhance radiation-induced cancer cell death. In line with this study, others demonstrated that overexpression of MnSOD suppressed cancer cell proliferation both in vitro and in mouse xenografts of human cancers (68,345,378). Mechanistically, the MnSOD-induced suppression of proliferation is probably associated with a delay in the progression from the G1 to the S phase (45,345).…”

Klotho Alleviates Lung Injury Caused by Paraquat via Suppressing ROS/P38 MAPK-Regulated Inflammatory Responses and Apoptosis

“…To detect apoptosis in situ of lung tissues, we used a terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) kit as our previous studies reported [22]. Briefly, lung tissue sections were dewaxed, rehydrated, and treated with proteinase K working solution for 30 min.…”

“…Counting Kit-8 (Beyotime, China) as we previously described [22]. The absorbance of each sample was measured by a microplate reader (SpectraMax, USA) at 450 nm.…”

“…Western Blotting Analysis. Total cellular proteins of each sample were separated by SDS-PAGE electrophoresis, and western blots were conducted as our previous study described [22]. The proteins were transferred onto polyvinylidene fluoride membranes.…”

MIIP gene expression is associated with radiosensitivity in human nasopharyngeal carcinoma cells

“…However, the accurate molecular mechanisms underlying their roles remain unclear. Several reports demonstrated that numerous tumor suppressor genes and oncogenes are associated with radiosensitivity (27)(28)(29)(30)(31)(32)(33). MIIP was first identified in a yeast two-hybrid screen for proteins that interact and inhibit insulin-like growth factor binding protein 2 (6).…”