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

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

目的:研究组蛋白去乙酰化酶抑制剂曲古抑菌素A(TSA)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;Western 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。

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-H3.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.