首页> 中文期刊> 《南方医科大学学报》 >多西他赛对雄激素依赖型及非依赖亚型前列腺癌细胞中C-jun与雄激素受体相互作用的影响

多西他赛对雄激素依赖型及非依赖亚型前列腺癌细胞中C-jun与雄激素受体相互作用的影响

         

摘要

Objective To investigate the effect of docetaxel on the interaction between C-jun and androgen receptor (AR) in prostate cancer LNCaP cells and its androgen-independence subtype LNCaP-bic cells. Methods LNCaP and LNCaP-bic cells were treated with docetaxel and the changes in AR and AP-1 expression were evaluated using ludferase assay. Western blotting and immunoprecipitation assay were employed to analyze the effects of docetaxel on the expressions of C-jun and AR and their interaction. Results Luciferase assay showed that LNCaP and LNCaP-bic cells expressed higher levels of AR and C-jun after docetaxel treatment. Docetaxel induced a higher level of p-c-jun expression in LNCaP-bic cells than in the parental LNCaP cells. Western blotting showed a strong PSA protein expression in LNCaP-bic cell after docetaxel treatment. Docetaxel caused a stronger interaction between AR and C-jun in LNCaP-bic cells. Conclusion Docetaxel activates ligand-independent AR transcription, and the interaction between AR and C-jun may affect the outcome of docetaxel chemotherapy.%目的 研究C-jun和雄激素受体(AR)在多西他赛处理的前列腺癌LNCaP细胞及其非雄激素依赖亚型LNCaP-bic细胞中的相互作用.方法 采用多西紫杉醇处理雄激素依赖型LNCaP的列腺癌细胞及其亚型雄激素非依赖型LNCaP-bic细胞,采用荧光素酶分析检测AR及AP-1基因的表达,利用Western blotting,免疫沉淀方法分析C-jun以及AR的蛋白表达和相互作用.结果 经多西他赛处理后,LNCaP-bic以及其父代LNCaP细胞AR和C-jun在基因表达水平均得到增强.Western blotting提示LNCaP-bic细胞中C-jun的磷酸化水平高于LNCaP细胞,同时其PSA蛋白表达也更强.免疫沉淀结果提示多西他赛使LNCaP-bic细胞株中的AR和C-jun有更高的相关作用.结论 多西他赛可以激活AR非配体依赖的转录功能,AR和C-jun之间的相互作用可能影响多西他赛对前列腺癌的化疗结果.

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