Targeting multiple signaling pathways in LNCaP prostate cancer cell line by trichostatin A / 中国临床药理学与治疗学

ABSTRACT

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.