琥珀酰亚胺基戊二酰胺酸诱导 320 HSR 结肠癌细胞凋亡和 G1 期阻滞。

Suberoylanilide hydroxamic acid induces apoptosis and sub-G1 arrest of 320 HSR colon cancer cells.

机构信息

Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taiwan, ROC.

出版信息

J Biomed Sci. 2010 Sep 17;17(1):76. doi: 10.1186/1423-0127-17-76.

BACKGROUND

Histone deacetylases and histone acetyl transferases covalently modify histone proteins, consequentially altering chromatin architecture and gene expression.

METHODS

The effects of suberoylanilide hydroxamic acid, a HDAC inhibitor, on 320 HSR colon cells were assessed in 320 HSR colon cancer cells.

RESULTS

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.

CONCLUSION

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.

背景

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。

方法

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。

结果

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。