Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taiwan, ROC.
J Biomed Sci. 2010 Sep 17;17(1):76. doi: 10.1186/1423-0127-17-76.
Histone deacetylases and histone acetyl transferases covalently modify histone proteins, consequentially altering chromatin architecture and gene expression.
The effects of suberoylanilide hydroxamic acid, a HDAC inhibitor, on 320 HSR colon cells were assessed in 320 HSR colon cancer cells.
Concentration and time-dependent inhibition of 320 HSR cell proliferation was observed. Treatment of 320 HSR cells with 5 μM SAHA for 72 h significantly inhibited their growth by 50% as compared to that of the control. Fluorescence-activated cell sorting analysis demonstrated significant inhibition of cell cycle progression (sub-G1 arrest) and induction of apoptosis upon various SAHA concentrations after 48 h. In addition, the anti-apoptosis proteins, survivin and Bcl-xL, were significantly inhibited by SAHA after 72 h of treatment. Immunocytochemistry analysis revealed that SAHA-resistant cells were positive for cyclin A (85%), ki-67 (100%), p53 (100%), survivin (100%), and p21 (90%) expression. Furthermore, a significant increase cyclin A-, Ki-67-, p53-, survivin-, and p21-positive cells were noted in SAHA-resistant tumor cells.
Our results demonstrated for the first time in 320 HSR colon adenocarcinoma cells that SAHA might be considered as an adjuvant therapy for colon adenocarcinoma.
组蛋白去乙酰化酶和组蛋白乙酰转移酶通过共价修饰组蛋白蛋白，从而改变染色质结构和基因表达。
在 320 HSR 结肠癌细胞中评估了琥珀酰亚胺基羟肟酸（一种 HDAC 抑制剂）对 320 HSR 结肠癌细胞的影响。
观察到浓度和时间依赖性抑制 320 HSR 细胞增殖。与对照组相比，用 5 μM SAHA 处理 320 HSR 细胞 72 h 可使细胞生长抑制 50%。荧光激活细胞分选分析表明，在不同的 SAHA 浓度下，细胞周期进程（亚 G1 期阻滞）和诱导凋亡在 48 h 后显著抑制。此外，在经过 72 h 的处理后，抗凋亡蛋白 survivin 和 Bcl-xL 也被 SAHA 显著抑制。免疫细胞化学分析显示，SAHA 耐药细胞对细胞周期蛋白 A（85%）、Ki-67（100%）、p53（100%）、survivin（100%）和 p21（90%）的表达呈阳性。此外，在 SAHA 耐药肿瘤细胞中，细胞周期蛋白 A、Ki-67、p53、survivin 和 p21 阳性细胞的数量显著增加。
我们的研究结果首次在 320 HSR 结肠腺癌细胞中表明，SAHA 可能被认为是结肠癌的辅助治疗药物。
