Department of Pathology, Tungs' Taichung MetroHarbor Hospital, Wuqi Township, Taichung County, Taiwan, Republic of China.
Pathol Oncol Res. 2012 Jul;18(3):713-20. doi: 10.1007/s12253-012-9499-7. Epub 2012 Jan 20.
We studied the effects of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, on colon cancer. The expression of HDACs in colorectal cancer specimens and the effects of SAHA on colon cancer cells and tumors of nude mice were assessed. Treatment with SAHA (3 μm) for 72 h induced downregulation of different subtypes of HDAC proteins and also induced acetylation of histone 3 and histone 4. SAHA significantly inhibited the expression of the oncogenic protein c-myc and also increased the expression of the p53 and Rb proteins. The immunohistochemical staining of HDACs, including HDAC1, HDAC2, HDAC3, and HDAC4, was significantly increased in colorectal adenocarcinoma specimens compared to healthy control tissues. In addition, murine studies showed that 100 mg/kg SAHA administered by intraperitoneal injection significantly induced tumor necrosis and inhibited the growth of colon tumors. Immunohistochemistry of the tumor tissues from nude mice revealed that SAHA inhibited the expression of different subtypes of histone deacetylase, the anti-apoptotic proteins cyclin D1, survivin, and also inhibited cell proliferative as determined by Ki67 expression. SAHA inhibited the growth of colon tumors by decreasing histone deacetylases and the expression of cyclin D1 and survivin in nude mice.
我们研究了琥珀酰亚胺基草酰苯胺（SAHA），一种组蛋白去乙酰化酶（HDAC）抑制剂，对结肠癌的影响。评估了 HDAC 在结直肠肿瘤标本中的表达以及 SAHA 对结肠癌细胞和裸鼠肿瘤的影响。用 SAHA（3μm）处理 72 小时诱导了不同亚型的 HDAC 蛋白的下调，也诱导了组蛋白 3 和组蛋白 4 的乙酰化。SAHA 显著抑制了致癌蛋白 c-myc 的表达，同时增加了 p53 和 Rb 蛋白的表达。与健康对照组织相比，结直肠腺癌标本中 HDACs（包括 HDAC1、HDAC2、HDAC3 和 HDAC4）的免疫组织化学染色明显增加。此外，鼠类研究表明，腹腔注射 100mg/kg 的 SAHA 可显著诱导肿瘤坏死并抑制结肠肿瘤的生长。裸鼠肿瘤组织的免疫组织化学分析表明，SAHA 抑制了不同亚型组蛋白去乙酰化酶、抗凋亡蛋白 cyclin D1、survivin 的表达，并通过 Ki67 表达抑制细胞增殖。SAHA 通过降低组蛋白去乙酰化酶和 cyclin D1、survivin 的表达来抑制裸鼠结肠肿瘤的生长。
