Disrupting SOD1 activity inhibits cell growth and enhances lipid accumulation in nasopharyngeal carcinoma

• Published in: Cell communication and signaling 2018-06, Vol.16 (1), p.28-13, Article 28
• Main Authors: Li, Shuai, Fu, Lanyan, Tian, Tian, Deng, Liwen, Li, Huangbin, Xia, Weixiong, Gong, Qing
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Antioxidants (Nutrients); Apoptosis; Breast cancer; Cancer therapies; Carnitine O-Palmitoyltransferase - metabolism; Cell growth; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; Cholecystokinin; Colorectal cancer; CPT1A; Enzymes; Fatty acids; Female; Gene expression; Gene Knockdown Techniques; Homeostasis; Humans; Hydrogen peroxide; Kaplan-Meier Estimate; Laboratory animals; Lipid Metabolism; Lipids; Metabolism; Mice; mRNA; Nasopharyngeal carcinoma; Nasopharyngeal Carcinoma - diagnosis; Nasopharyngeal Carcinoma - genetics; Nasopharyngeal Carcinoma - metabolism; Nasopharyngeal Carcinoma - pathology; Oxidation; Prognosis; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; ROS; SOD1; Superoxide; Superoxide dismutase; Superoxide Dismutase-1 - deficiency; Superoxide Dismutase-1 - genetics; Superoxide Dismutase-1 - metabolism; Throat cancer; Triglycerides; Western blotting; Xenografts
• ISSN: 1478-811X; 1478-811X
• DOI: 10.1186/s12964-018-0240-3

SOD1 is an abundant enzyme that has been studied as a regulator of the antioxidant defence system, and this enzyme is well known for catalyzing the dismutation of superoxide into hydrogen peroxide. However the SOD1 in the progress of NPC and underlying mechanisms remain unclear. In NPC tissue samples, SOD1 protein levels were measured by Western blot and immunohistochemical (IHC) staining. mRNA levels and SOD1 activity were monitored by qRT-PCR and SOD activity kit, respectively. Kaplan-Meier survival analysis was performed to explore the relationship between SOD1 expression and prognosis of NPC. The biological effects of SOD1 were investigated both in vitro by CCK-8, clonogenicity and apoptosis assays and in vivo by a xenograft mice model. Western blotting, ROS assay and triglyceride assays were applied to investigate the underlying molecular mechanism of pro-survival role of SOD1 in NPC. We observed a significant upregulation of SOD1 in NPC tissue and high SOD1 expression is a predictor of poor prognosis and is correlated with poor outcome. We confirmed the pro-survival role of SOD1 both in vitro and in vivo. We demonstrated that these mechanisms of SOD1 partly exist to maintain low levels of the superoxide anion and to avoid the accumulation of lipid droplets via enhanced CPT1A-mediated fatty acid oxidation. The results of this study indicate that SOD1 is a potential prognostic biomarker and a promising target for NPC therapy.