Department of Pharmacology, National Medicines Institute, Warsaw, Poland.
Eur J Pharmacol. 2010 Feb 10;627(1-3):26-32. doi: 10.1016/j.ejphar.2009.10.033. Epub 2009 Oct 22.
Histone deacetylases (HDACs) activity determines the acetylation status of histons, and has the ability to regulate gene expression through chromatin remodelling. HDACs are a promising target for pharmacological inhibition, since it has been discovered that some genes are repressed by their inappropriate recruitment. To test this we have addressed the hypothesis that histone deacetylase inhibitors SBHA and MS275 potentiate inhibitory effects of classical anti-colorectal cancer cytostatic, 5-fluorouracil (5-FU), on survival of colorectal cancer (CRC) cells in vitro. We are reporting here that HDAC inhibitors show potent synergistic interaction with 5-FU. The observed synergism between HDAC inhibitors and 5-FU is most probably related to the augmented apoptotic signal allowed for significant (both biological and statistical) reduction of the cytotoxic doses.
组蛋白去乙酰化酶 (HDACs) 的活性决定了组蛋白的乙酰化状态，并且具有通过染色质重塑调节基因表达的能力。HDACs 是药物抑制的一个有前途的靶点，因为已经发现某些基因通过其不适当的募集而受到抑制。为了检验这一点，我们提出了一个假设，即组蛋白去乙酰化酶抑制剂 SBHA 和 MS275 增强了经典抗结直肠癌细胞生长抑制药物 5-氟尿嘧啶 (5-FU) 对结直肠癌细胞 (CRC) 体外存活的抑制作用。我们在这里报告说，HDAC 抑制剂与 5-FU 表现出强大的协同作用。观察到的 HDAC 抑制剂与 5-FU 之间的协同作用很可能与增强的凋亡信号有关，这使得细胞毒性剂量显著（在生物学和统计学上）降低。
