SAHA Inhibits the Growth of Colon Tumors by Decreasing Histone Deacetylase and the Expression of Cyclin D1 and Survivin
SAHA Inhibits the Growth of Colon Tumors by Decreasing Histone Deacetylase and the Expression of Cyclin D1 and Survivin
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DOI：
10.1007/s12253-012-9499-7
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发表时间：
2012-07-01
影响因子：
2.8
通讯作者：
Tzao, Ching
中科院分区：
文献类型：
--
作者：
Jin, Jong-Shiaw;Tsao, Tang-Yi;Tzao, Ching
我们研究了组蛋白脱乙酰酶(HDAC)抑制剂--琥珀酰苯胺异羟肟酸(SAHA)对结肠癌的作用。观察HDACs在结直肠癌标本中的表达及SAHA对结肠癌细胞和裸鼠肿瘤的影响。SAHA(3MU M)作用72 h可诱导不同亚型HDAC蛋白表达下调，并诱导组蛋白3和组蛋白4乙酰化。SAHA可显著抑制癌基因蛋白c-myc的表达，并上调p53和Rb蛋白的表达。大肠腺癌组织中HDAC1、HDAC2、HDAC3和HDAC4的免疫组织化学染色均显著高于正常组织。此外，小鼠研究表明，腹腔注射100 mg/kg的SAHA可显著诱导肿瘤坏死并抑制结肠肿瘤的生长。裸鼠肿瘤组织免疫组织化学结果显示，SAHA可抑制不同亚型的组蛋白脱乙酰酶、抗凋亡蛋白Cyclin D1、Survivin的表达，并能抑制Ki67的表达，抑制细胞增殖。SAHA通过降低组蛋白脱乙酰酶及细胞周期蛋白D1和Survivin的表达，抑制裸鼠结肠癌的生长。
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 mu m) 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.