The effect on radioresistance of manganese superoxide dismutase in nasopharyngeal carcinoma

Abstract

Abstract. Failure to control nasopharyngeal carcinomas (NPC) is mainly due to a portion of radioresistant phenotype. Identifying gene targets for radiosensitization is an important strategy in improving anticancer treatments. Exposure of cells to ionizing radiation leads to the formation of reactive oxygen species that are associated with radiation-induced cellular apoptosis and necrosis. The antioxidant enzyme manganese superoxide dismutase (SOD2) catalyzes the dismutation of the superoxide anions into hydrogen peroxide. We reasoned that SOD2 could contribute to the radioresistant phenotype in NPC cells. We compared CNE1 cells with CNE2 cells in radiation character and SOD2 protein. SOD2 gene silencing through the plasmid transfer using a microRNA interference optimized for transcription in NPC cell lines inhibited the radioresistance of human NPC cells. We compared radioresistant NPC with radiosensitive NPC in SOD2 expression. CNE1 cells and CNE2 cells demonstrated dose-modifying factors at 10% isosurvival of 1.529 and 1. CNE1 cells were 1.94-fold higher than CNE2 cells at SOD2 protein baseline, and CNE1 cells exposed to ionizing radiation demonstrated 1.15-to 1.39-fold increase in SOD2 immunoreactive protein. Radioresistance in CNE1 cells was reduced following expression of miRNA targeting SOD2. Radioresistant tumors (11/23) were SOD2-positive, and 2/46 radiosensitive tumors were SOD2-positive before commencement of radiotherapy. The results presented suggest that SOD2 expression can participate in radioresistance of NPC, being markers of a subset of tumors in which routine radiation treatment failure is likely. Combination of the SOD2 gene silencing therapy and conventional radiotherapy should be attempted to improved cancer therapy for NPC.

Dual Characters of GH-IGF1 Signaling Pathways in Radiotherapy and Post-radiotherapy Repair of Cancers

“…Reactive oxygen species level and the balance of ROS level in cancer cells are important in radio-resistance ( Reuter et al, 2010 ). Therefore, radiation tends to induce ROS levels and adaptive antioxidant defense systems, which may lead to radio-resistance ( Riley, 1994 ; Guo et al, 2003 ; Qu et al, 2010 ). Persistent oxidative stress regulates many transcription factors/activators, such as NF-κB and p53, thereby influencing the cell cycle and DNA repair signaling pathways ( Reuter et al, 2010 ).…”

Fitter Mitochondria Are Associated With Radioresistance in Human Head and Neck SQD9 Cancer Cells

“…Some radioresistant HNSCC cancer cells can also overexpress glucose transporters (GLUTs) or glycolytic enzymes to promote glucose metabolism instead of glutamine metabolism, which is associated to fast energy production and biosynthesis for cell survival and repair (Yan et al, 2013;Mims et al, 2015;Jung et al, 2017). Mitochondria can further modulate radiosensitivity by fine-tuning the activity of superoxide dimutases (SODs) and ROS production (Qu et al, 2010;Holley et al, 2014;Li et al, 2017). Lipid metabolism (Mims et al, 2015) and autophagy (Moergel et al, 2010;Kuwahara et al, 2011) have also been proposed as contributors to radioresistance.…”