曲古抑菌素A对前列腺癌LNCaP细胞抑制效应的细胞信号通路研究

目的：研究组蛋白去乙酰化酶抑制剂曲古抑菌素A（1SA）对前列腺癌LNCaP细胞抑制作用的细胞信号机制。方法：半固体培养检测TSA对前列腺癌细胞集落形成能力的影响；Westem Blot分析细胞蛋白乙酰化水平、细胞信号通路蛋白及细胞周期相关蛋白的表达。结果：TSA能够有效杀伤前列腺癌LNCaP细胞，在较低浓度即能抑制具有集落形成能力的细胞；药物处理使细胞内蛋白乙酰化水平增高，乙酰化组蛋白H3积累，多种细胞信号通路的相关蛋白如雄激素受体、HER2、Raf-1、Akt、CDK4等呈时间依赖性和剂量依赖性被清除。结论：TSA能够同时阻断对细胞生长具有重要作用的多条细胞信号通路，从而对前列腺癌LNCaP细胞发挥抑制作用。

Targeting multiple signaling pathways in LNCaP prostate cancer cell line by trichostatin A

AIM: To investigate the molecular mechanisms underlying the antitumor effect of trichostatin A(TSA) on LNCaP prostate cancer cells.METHODS: Colony formation analysis was performed to assay the effect of TSA on LNCaP colony forming ability.Western blotting was used to analyze protein acetylation standard as well as the expression of a panel of signaling molecules after TSA exposure.RESULTS: TSA inhibited the colony forming ability of LNCaP cells at a very low concentration.TSA exposure caused elevated acetylation of total cellular proteins as well as accumulation of acetylated-H_3.In addition,signaling molecules which play key roles in prostate cancer such as AR,ErbB2,Raf-1,CDK4,and Akt were depleted by TSA in a dose and time-dependent manner.CONCLUSION: TSA exhibits significant antitumor activity against LNCaP cells by simultaneously interfering with multiple signaling pathways such as HER2/MAPK,AR,and PI-3K-AKT pathways.