Ku80在人肺癌中的表达水平与放疗前后表达变化的实验研究

Ku80 expression in lung cancer patients and nude mice bearing human lung carcinoma before and after irradiation

目的基于Ku80在辐射诱导的DNA修复中的作用,研究不同病理类型肺癌中Ku80的表达水平,并以人肺癌A549细胞接种裸鼠模型评估放疗对Ku80表达的影响。方法使用免疫组化及荧光定量PCR分别检测不同病理类型肺癌Ku80蛋白和mRNA的表达水平。将A549细胞接种到裸鼠上再以不同剂量的射线照射,并分别在24、48h后处死,用免疫组化及荧光定量PCR检测Ku80蛋白和mRNA的表达水平。结果肺癌组织表达的Ku80蛋白、mRNA水平高于正常肺组织(均P<0.01)。在肺癌亚组中,肺腺癌和鳞癌比小细胞肺癌表达更高的Ku80蛋白、mRNA水平(均P<0.01)。接种在裸鼠的人肺癌A549细胞经过不同剂量射线照射后Ku80 mRNA的表达增加,并具有剂量和时间依赖性。结论 Ku80在放疗引起的DNA破坏过程中起到重要的作用。肺鳞癌和腺癌的Ku80表达高于小细胞肺癌,这可能是肺鳞癌和腺癌放射敏感性逊于小细胞肺癌的原因之一。Ku80表达水平可能在预测肺癌的放射敏感性方面具有重要价值,可以成为肺癌放射增敏治疗的一个新靶点。

Objective To investigate Ku80 expression in lung cancer patients and nude mice bearing human lung carci-noma before and after irradiation. Methods Cancer tissue and pericancerous tissue specimens were col ected from 24 lung cancer patients, including 10 cases of lung adenocarcinoma,8 cases of lung squamous carcinoma and 6 cases of smal- celllung carcinoma. Human lung cancer A549 cells were inoculated in BALB/c nude mice and the tumor- bearing mice were ex-posed to varying doses of irradiation. Immunohistochemistry and real- time PCR were applied to determine Ku80 protein and mRNA expression, respectively. Results Lung carcinoma tissue exhibited higher Ku80 mRNA and protein levels when com-pared with normal tissue （P＆lt;0.01）. Lung adenocarcinoma and lung squamous carcinoma showed higher levels of Ku80 protein and mRNA, compared with smal- celllung carcinoma （P＆lt;0.01）. There was a dose- dependent and time- dependent increase in Ku80 mRNA levels in tumor- bearing nude mice exposed to varying doses of irradiation. Conclusion Ku80 may be involved in DNA damage repairing, and higher Ku80 levels in non- smal celllung cancer may be associated with its lower radiosensitivi-ty. The results indicated that Ku80 expression levels could be useful in predicting radiosensitivity of lung cancer and Ku80 may be used as a target to improve radiosensitivity in lung cancer patients.