RESUMO
BACKGROUND: Radioresistance leads to treatment failure in patients with nasopharyngeal carcinoma (NPC). Thus, enhancing the radiosensitivity of NPC cells would likely increase the effectiveness of radiotherapy. Annexin VII (Annexin A7, ANXA7) might be a tumor promoter in NPC but its functions in radiosensitivity remain unclear. METHODS: NPC cell lines CNE2-shANXA7 and CNE2-pLKO.1 were generated and CNE2-shANXA7 nude mice xenograft tumor models were established. The main effects and molecular mechanisms of ANXA7 knockdown in NPC radiosensitivity were studied in vitro and in vivo by analyzing cell viability, clonogenicity, apoptosis, cell cycle distribution, tumor radioresponse and immunohistochemistry assay. RESULTS: ANXA7 knockdown revealed potentially enhanced NPC cell radiosensitivity via apoptosis and increased the cell number at the G2/M phase. In the xenograft model, NPC cells with ANXA7 knockdown were dramatically sensitive to irradiation and tumor growth was significantly suppressed. Compared to CNE2-pLKO.1 xenografts, CNE2-shANXA7 showed more γ-H2AX foci and less phospho-DNA PKcs. CONCLUSIONS: ANXA7 knockdown increased the radiosensitivity of NPC by enhancing apoptosis, modulating the cell cycle distribution into more radiosensitive phases, promoting DNA damage, and inhibiting repair. We showed that decreased ANXA7 levels enhanced radiosensitivity and provided insights into the therapeutic targets for NPC radiotherapy.
Assuntos
Anexina A7/metabolismo , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Animais , Anexina A7/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Ciclo Celular/genética , Ciclo Celular/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Dano ao DNA/genética , Dano ao DNA/efeitos da radiação , Reparo do DNA/genética , Reparo do DNA/efeitos da radiação , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Nasofaringe/patologia , RNA Interferente Pequeno/metabolismo , Tolerância a Radiação/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND Symptom distress is very common in patients with nasopharyngeal carcinoma (NPC) during radiotherapy, seriously affecting their quality of life and impeding the process of rehabilitation. Resourcefulness training can enhance the level of resourcefulness and benefit-finding, palliate symptom distress, and promote disease rehabilitation. However, the effects of resourcefulness training on local complications and benefit-finding in NPC patients during radiotherapy remains poorly understood. MATERIAL AND METHODS Questionnaires and resourcefulness training intervention were used in this study. The relationships among resourcefulness, benefit-finding, and symptom distress of 304 NPC patients were analyzed and the effects of resourcefulness training on NPC patients (N=80) were evaluated during radiotherapy. RESULTS Among the 304 NPC patients, age, educational level, occupation, family monthly income, method of payment of medical expenses, and histological types were significant factors influencing resourcefulness and benefit-finding. The patients' resourcefulness was positively correlated to their benefit-finding; and their distress was negatively correlated to their resourcefulness. After resourcefulness training for 2 months, average scores of the resourcefulness and benefit-finding were significantly increased in the intervention group (N=40) compared to those in the control group (N=40). Average scores of symptom distress were significantly reduced in the 2 groups, but they were reduced more significantly in the intervention group than in the control group. CONCLUSIONS The patients' benefit-finding and symptom distress were correlated with their resourcefulness. Resourcefulness training could enhance the level of resourcefulness and benefit-finding, palliate symptom distress, and promote disease rehabilitation in NPC patients during radiotherapy.
