塞来昔布对非小细胞肺癌移植瘤的辐射增敏实验研究

目的 建立裸鼠非小细胞肺癌H460细胞动物模型，观察环氧化酶2选择性抑制剂塞来昔布对H460放疗的增敏作用，并对其作用机理进行初步探讨。 方法 将40只荷瘤鼠用完全随机法分成4组，分别为空白对照组、放疗组、塞来昔布组、塞来昔布+放疗组，每组10只。采用灌肠法给予塞来昔布16 mg·kg-1·d-1，给药2 h后进行放疗，放疗分割剂量为5 Gy/次，2次/周，4周后处死所有荷瘤鼠，解剖瘤块称重。采用免疫组化方法分析毛细血管扩张性共济失调症突变蛋白（ATM）和表皮生长因子受体（EGFR）表达的变化。 结果 空白对照组、塞来昔布组、放疗组、塞来昔布+放疗组肿瘤瘤重分别为（133.62±12.37）、（130.37±12.59）、（81.17±8.29）、（35.51±4.23）mg，塞来昔布+放疗组与放疗组比较差异有统计学意义（t=5.41，P < 0.01）。塞来昔布+放疗组的ATM和EGFR表达水平明显降低，与放疗组比较差异有统计学意义（t=4.23和3.17，P均 < 0.01）。 结论 塞来昔布可能通过降低ATM和EGFR的表达水平，增强H460细胞的放疗敏感性，将来可能具有较好的临床应用价值。

Radiosensitization on non-small cell lung cancer induced by celecoxib

Objective To establish the nude mice model of non-small cell lung cancer(NSCLC)H460 cell to investigate the combined effects of radiotherapy and celecoxib. Methods Athymic mice bearing H460 were randomly divided into 4 groups:control, radiotherapy, celecoxib and radiotherapy plus celecoxib group. The administration dose of celecoxib was 16 mg·kg-1·d-1. The mice were treated with radiotherapy 2 hours after administration and the fractionated dose was 5 Gy, 2 fractions per week. Mice were killed to detect tumor weight 4 weeks after treatment. The expression levels of ataxia telangiectasis mutated(ATM)and epidermal growth factor receptor(EGFR)in tumor tissues were detected by immune-histochmical method. Results The tumor weight in control, radiotherapy, celecoxib and radiotherapy plus celecoxib group were(133.62±12.37), (130.37±12.59), (81.17±8.29) and (35.51±4.23)mg respectively. There was significant difference between the radiotherapy plus celecoxib group and the radiotherapy group(t=5.41, P < 0.01). The expression levels of ATM and EGFR in the radiotherapy plus celecoxib group were significantly lower than that in radiotherapy group(t=4.23 and 3.17, both P < 0.01). Conclusions Celecoxib promotes radiotherapeutic sensitivity of H460 by down-regulating the expression levels of ATM and EGFR. Celecoxib may presents potency in curing human lung cancer.