【摘要】 目的设计反义ATM(共济失调毛细血管扩张症突变基因)多核苷酸作用于裸鼠移植瘤以探讨其对喉鳞状细胞癌(Hep-2)放射治疗敏感性的影响。方法①雌性BALB/c-nu/nu裸鼠,分成对照组、ATM AS-ODNs(ATM反义多核苷酸)组、单独放疗组、ATM AS-ODNs+放疗4组(联合治疗组),每组8只,于裸鼠背侧部皮下注射105个Hep-2细胞悬液并对各组进行相应处理;②3周后用Western blot对各组瘤体的ATM蛋白进行分析;③用TUNEL染色法检测各组瘤体中细胞凋亡情况。结果①与ATM AS-ODNs组比较,AS-ODNs+放疗组的ATM蛋白表达量降低[(76.84±3.12)%vs(48.19±3.98)%,P<0.05]。②ATM AS-ODNs+放疗组的细胞凋亡数显著高于单独放疗组、AS-ODNs组及对照组[(17.12±4.2)%vs(8.17±3.5)%,(4.13±2.3)%,(3.09±5.3)%],差异有统计学意义。③采用AS-ODNs+放疗组的肿瘤生长较ATM AS-ODNs组、放疗组及对照组慢。结论反义ATM多核苷酸在体内增强了喉鳞状细胞癌对放射治疗的敏感性。更多还原

【Abstract】 Objective To investigate the effect of the antisense polynucleotide(AS-ODNs)targeting ataxia telangiectasia mutated(ATM)on radiosensitivity to the transplanted tumors of nude mice in laryngeal squamous cell carcinoma cell line(Hep-2).Methods ①Female BALB/c-nu/nu mice were randomized into four groups(n=8 in each group).The mice were treated with normal saline in control group and ATM AS-ODNs alone in ATM ASODNs group.The mice were exposed to X-ray of 2 Gy alone in radiation group,while in ATM AS-ODNs+radiotherapy group,2.5 mg/kg of ATM AS-ODNs was injected into the solid tumor the day before exposure to 2 Gy X-ray,and repeated again at an interval of 5 d for each time.About 1×105 Hep-2 cells were subcutaneously inoculated in dorsal space of the mice.②The expression of ATM protein in tumor was examined by Western blot in four groups after 3 weeks.③TUNEL assay was used to analyze the cell apoptosis in the tumors of nude mice.Results ①The ATM protein expression in AS-ODNs+radiotherapy group was significantly lower than that in AS-ODNs group [(48.19±3.98)% vs(76.84±3.12)%,P<0.05].②The apoptotic cells was statistically higher in AS-ODNs+radiotherapy group than those in the other groups(P<0.05).③Tumor growth rate was slower in AS-ODNs+radiotherapy group than that of ATM AS-ODNs group,radiation group and control group.Conclusion ATM AS-ODNs could strengthen the radiosensitivity of laryngeal cell carcinoma in vivo.更多还原