Department of Urology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
BJU Int. 2010 Apr;105(8):1181-6. doi: 10.1111/j.1464-410X.2009.08795.x. Epub 2009 Aug 13.
To examine the expression profile of histone deacetylase (HDAC)-1 and explore its potential role in the development of bladder cancer, using valproic acid (VPA), a HDAC inhibitor, which reduces tumour growth and metastasis formation in animal models.
The study comprised clinical samples from patients with urinary bladder cancer, mouse urinary bladder tissue specimens, and two human urinary bladder cancer cell lines (HT-1376 and 5637). HDAC1 mRNA and protein expression were examined using real-time reverse transcription-polymerase chain reaction and immunohistochemical methods. Female C3H/He mice were given VPA (0, 250, 500 and 750 mg/kg body weight, intraperitoneal, every day) from the start or 4 weeks after 0.05%N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) treatment, and were humanely killed and sampled at 8 and 12 weeks.
A significantly higher level of HDAC1 mRNA was expressed in human urinary bladder cancer specimens. The immunohistochemical study showed that HDAC1 was expressed in the cytoplasm and nucleus in the specimens. BBN treatment increased HDAC1 mRNA expression in the urinary bladder. VPA administration seemed to delay the incidences of BBN-induced mouse urinary bladder tumour, possibly through p21(WAF1) protein expression.
These results indicate that HDAC might be an effective molecular target for cancer therapy.
使用组蛋白去乙酰化酶 (HDAC)-1 抑制剂丙戊酸 (VPA) 研究 HDAC-1 的表达谱，并探索其在膀胱癌发展中的潜在作用。VPA 在动物模型中可降低肿瘤生长和转移形成。
本研究包括膀胱癌患者的临床样本、小鼠膀胱组织标本和两种人膀胱癌细胞系 (HT-1376 和 5637)。使用实时逆转录聚合酶链反应和免疫组织化学方法检测 HDAC1 mRNA 和蛋白质表达。从开始或在 0.05%N-丁基-N-(4-羟基丁基)-亚硝胺 (BBN) 处理后 4 周起，雌性 C3H/He 小鼠每天腹膜内给予 VPA (0、250、500 和 750mg/kg 体重)，并在 8 和 12 周时人道处死和取样。
人膀胱癌标本中 HDAC1 mRNA 表达水平显著升高。免疫组织化学研究显示 HDAC1 在标本中表达于细胞质和细胞核。BBN 处理增加了膀胱中的 HDAC1 mRNA 表达。VPA 给药似乎通过 p21(WAF1) 蛋白表达延迟了 BBN 诱导的小鼠膀胱肿瘤的发生。
这些结果表明 HDAC 可能是癌症治疗的有效分子靶点。
