title: Bidirectional regulation of manganese superoxide dismutase (MnSOD) on the radiosensitivity of esophageal cancer cells.
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.
authors.affiliation: Department of Chemoradiotherapy, Tangshan People's Hospital, Tangshan, China.
authors.forename: Guo-Gui
authors.initials: GG
authors.lastname: Sun
authors.forename: Wan-Ning
authors.initials: WN
authors.lastname: Hu
authors.forename: Ya-Di
authors.initials: YD
authors.lastname: Wang
authors.forename: Cong-Rong
authors.initials: CR
authors.lastname: Yang
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Lu
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000532:radiotherapy*; D048708:Cell Growth Processes / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000235:genetics; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D006801:Humans; D009569:Nitric Oxide / Q000235:genetics / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D011836:Radiation Tolerance; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D014162:Transfection / Q000379:methods
chemical_list: D018076:DNA, Complementary; D017382:Reactive Oxygen Species; D009599:Nitroprusside; D009569:Nitric Oxide; D013482:Superoxide Dismutase