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http://dx.doi.org/10.7314/APJCP.2012.13.7.3015

Bidirectional Regulation of Manganese Superoxide Dismutase (MnSOD) on the Radiosensitivity of Esophageal Cancer Cells  

Sun, Guo-Gui (Department of Chemoradiotherapy, Tangshan People's Hospital)
Hu, Wan-Ning (Department of Chemoradiotherapy, Tangshan People's Hospital)
Wang, Ya-Di (Department of Radiotherapy, The Military General Hospital of Beijing PLA)
Yang, Cong-Rong (Department of Radiotherapy, The Fourth Hospital of Hebei Medical University)
Lu, Yi-Fang (Department of Endocrinology, Tangshan Workers Hospital)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.7, 2012 , pp. 3015-3023 More about this Journal
Abstract
The mitochondrial antioxidant protein manganese superoxide dismutase (MnSOD) may represent a new type of tumor suppressor protein. Overexpression of the cDNA of this gene by plasmid or recombinant lentiviral transfection in various types of cancer leads to growth suppression both in vitro and in vivo. We previously determined that changes in MnSOD expression had bidirectional effects on adriamycin (ADR) when combined with nitric oxide (NO). Radiation induces free radicals in a manner similar to ADR, so we speculated that MnSOD combined with NO would also have a bidirectional effect on cellular radiosensitivity. To examine this hypothesis, TE-1 human esophageal squamous carcinoma cells were stably transfected using lipofectamine with a pLenti6-DEST plasmid containing human MnSOD cDNA at moderate to high overexpression levels or with no MnSOD insert. Blastidicin-resistant colonies were isolated, grown, and maintained in culture. We found that moderate overexpression of MnSOD decreased growth rates, plating efficiency, and increased apoptosis. However, high overexpression increased growth rates, plating efficiency, and decreased apoptosis. When combined with NO, moderate overexpression of MnSOD increased the radiosensitivity of esophageal cancer cells, whereas high MnSOD overexpression had the opposite effect. This finding suggests a potential new method to kill certain radioresistant tumors and to provide radioresistance to normal cells.
Keywords
Manganese superoxide dismutase; nitric oxide; esophageal carcinoma; reactive oxygen species;
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