摘要
目的探讨多西紫杉醇的细胞毒性化疗反应的分子机制.方法对体外的免疫印迹、荧光素酶和细胞生存率进行分析,研究PC-3细胞暴露在多西紫杉醇后p-c-jun的过表达与AR的相互作用.结果多西紫杉醇治疗PC-3细胞最敏感,细胞对多烯紫杉醇的敏感性与p-c-jun水平呈负相关.转染c-jun基因转染到PC-3细胞降低了多烯紫杉醇的敏感性,而转染c-jun和AR基因则可以恢复到中等程度敏感性.p-c-jun与AR蛋白水平之间没有发现直接相关性.对多烯紫杉醇的治疗反应,体内模型的结果与体外研究结果是一致的.结论 p-c-jun可能是多西紫杉醇对前列腺癌治疗的分子机制之一.
Objective To investigate the molecular mechanism of Docetaxel in treatment of PCa by detecting the expression of androgen receptor（AR）and p-jun in PC-3 cells treated with Docetaxel.Methods The effect of c-Jun overexpression and its interaction with AR upon PC-3 cells exposure to Docetaxel were studied in vitro by immunobloting,luciferase and viability assays and in vivo using xenograft mice model.Furtheremore,the expression of c-jun and p-c-jun in xenograft mice tissues was investigated by immunohistochemistry.Results PC-3 cells were most sensitive to docetaxel treatment.The sensitivity of PC-3 cells to docetaxel was negatively correlated with the phosphorylation level of c-jun.Transfection with c-Jun gene into PC-3 cells decreased the sensitivity to doctexel treatment whereas cotransfection of c-jun and AR restored the sensitivity to a moderate degree.No direct correlation was found between the level of p-c-Jun and AR.The response to docetaxel treatment in vivo model was comparable to the in vitro results.Conclusion The phosphorylation level of c-Jun may be one of the mechanisms of docetaxel in treatment of prostate cancer.
出处
《昆明医科大学学报》
CAS
2012年第11期26-31,共6页
Journal of Kunming Medical University
基金
云南省卫生厅科研基金资助项目(2010NS053)
