Background: Stanniocalcin 2 (STC2) expression is upregulated under multiple stress conditions including hypoxia, nutrient starvation and radiation. Overexpression of STC2 correlates with tumor progression and poor prognosis. Purpose: We previously demonstrated that overexpression of STC2 in nasopharyngeal carcinomas (NPC) positively correlates with radiation resistance and tumor metastasis, two major clinical obstacles to the improvement of NPC management. However, it remains elusive whether STC2 expression is a critical contributing factor for post-radiation survival and metastasis of NPC cells. Materials and methods: Using the radiation resistant CNE2 cell line as a model, we examined the importance of STC2 expression for post-radiation survival, migration and invasion. Here, we report the establishment of STC2 knockout lines (CNE2-STC2-KO) using the CRISPR/Cas9-based genome editing technique. Results: Compared with the parental line, STC2-KO cells showed similar proliferation and morphology in normal culture conditions, and loss of STC2 did not compromise the cell tumorigenicity in nude mice model. However, STC2-KO lines demonstrated increased sensitivity to X-radiation under either normoxic or hypoxic conditions. Particularly, upon X-radiation, parental CNE2 cells only slightly whereas STC2-KO cells remarkably decreased the migration and invasion ability. Cell cycle analysis revealed that loss of STC2 accumulated cells in G₁ and G₂/M phases but decreased S-population. Conclusion: These data indicate that the expression of STC2, which can be stimulated by metabolic or therapeutic stresses, is one important factor to promote survival and metastasis of post-radiation NPC cells. Therefore, targeting STC2 or relative downstream pathways may provide novel strategies to overcome radiation resistance and metastasis of NPC.

Background: Paraspeckle component 1 (PSPC1) is overexpressed in various cancer and correlated with poor survival in the patients. However, little is known about its expression and role in the progression of nasopharyngeal carcinomas (NPC). The purpose of this study is to examine PSPC1 expression in NPC and explore its role in clinical prognosis of radiation therapy. Methods: The association of PSPC1 expression with clinicopathological features of 109 NPC patients was examined using partial correlation analysis. Cancer tissues were obtained prior to clinical treatment. All cases were diagnosed and pathologically confirmed to be poorly differentiated or undifferentiated NPC without distant metastasis. The patients were then treated with radiation and followed-up. Survival analysis was performed. Results: Partial correlation analysis revealed that the PSPC1 expression in NPC was correlated with N classification, recurrence, prognosis and radiosensitivity in NPC patients, but not with the gender, age, pathohistological pattern, clinical stage, and T classification. The overexpression of PSPC1 was detected in 64 samples (58.72%). Kaplan–Meier survival analysis revealed that the overall survival (OS) was longer in NPC patients with PSPC1 low expression than that in those with PSPC1 high expression. Moreover, patients with the overexpression of PSPC1 had a low progression-free survival and distant metastasis-free survival rate, compared to those who had a low expression of PSPC1. Although not statistically significant, patients with high expression of PSPC1 had a lower locoregional recurrence-free survival rate than those with low expression, and the curves between the two groups was well separated. Conclusion: PSPC1 overexpression was associated with poor prognosis for NPC, which might be a novel useful biomarker to predict the response of NPC to radiation therapy and its clinical outcome.

GST‐TAT‐SOD was the fusion of superoxide dismutase (SOD), cell‐permeable peptide TAT, and glutathione‐S‐transferase (GST). It was proved to be a potential selective radioprotector in vitro in our previous work. This study evaluated the in vivo radioprotective activity of GST‐TAT‐SOD against whole‐body irradiation. We demonstrated that intraperitoneal injection of 0.5 ml GST‐TAT‐SOD (2 kU/ml) 2 h before the 6 Gy whole‐body irradiation in mice almost completely prevented the splenic damage. It could significantly enhance the splenic antioxidant activity which kept the number of splenic white pulp and consequently resisted the shrinkage of the spleen. Moreover, the thymus index, hepatic antioxidant activity, and white blood cell (WBC) count of peripheral blood in irradiated mice pretreated with GST‐TAT‐SOD also remarkably increased. Although the treated and untreated irradiated mice showed no significant difference in the growth rate of animal body weight at 7 days postirradiation, the highest growth rate of body weight was observed in the GST‐TAT‐SOD‐pretreated group. Furthermore, GST‐TAT‐SOD pretreatment increased resistance against 8 Gy whole‐body irradiation and enhanced 30 d survival. The overall effect of GST‐TAT‐SOD seemed to be a bit more powerful than that of amifostine. In conclusion, GST‐TAT‐SOD would be a safe and potentially promising radioprotector.

GST‐TAT‐SOD, a cell‐permeable bifunctional antioxidant enzyme, is a potential selective radioprotector. This study aimed to investigate the cytoprotective activity of GST‐TAT‐SOD against cisplatin‐induced damage. The current study showed that cisplatin induced the formation of reactive oxygen species in normal L‐02 cells. GST‐TAT‐SOD (2000 U/mL) executed its antioxidant role by directly scavenging excess intracellular free radicals and augmenting cellular antioxidant defense such as reducing MDA level, enhancing the SOD activity, GST activity, and T‐AOC. Thus, it suppressed the growth inhibition and apoptosis of cisplatin‐treated normal cells. Meanwhile, the growth inhibition of tumor cells (SMMC‐7721) caused by cisplatin was unaffected by GST‐TAT‐SOD pretreatment. GST‐SOD, as a comparison, seemed to be powerless for related indicators as it could not enter into cells without cell‐permeating peptide. These results suggest that GST‐TAT‐SOD might be a potential cytoprotective agent for cisplatin‐induced side effects.