组蛋白去乙酰化酶抑制剂FK228对N-丁基-N-(4-羟基丁基)亚硝胺诱导的p53+/-和p53+/+小鼠膀胱癌发生缺乏预防作用。
Lack of preventive efficacy of FK228, a histone deacetylase inhibitor, against N-butyl-N-(4-hydroxybutyl) nitrosamine-induced urinary bladder carcinogenesis in p53+/- and p53+/+ mice.
作者信息
Wei Min, Wanibuchi Hideki, Morimura Keiichirou, Salim Elsayed I, Moku Masaharu, Doi Kenichiro, Mitsuhashi Makoto, Masuda Chikayoshi, Shen Jun, Kinoshita Anna, Fukushima Shoji
机构信息
Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
出版信息
Anticancer Res. 2004 Mar-Apr;24(2B):785-90.
BACKGROUND
The efficacy of FK228, a histone deacetylase inhibitor that is currently under early clinical trials for cancer therapy, against N-butyl-N-(4-hydroxybutyl)- nitrosamine (BBN) -induced mouse urinary bladder carcinogenesis was examined.
MATERIALS AND METHODS
Heterozygous p53-deficient (p53+/-) and wild-type (p53+/+) mice were given FK228 (0, 0.01 and 0.1 mg/kg i.p., 3 times/week, respectively) after 10 weeks of 0.05% BBN treatment, and were sacrificed at 22 and 24 weeks after the start, respectively.
RESULTS
There was no significant difference in the incidence of urinary bladder tumors among groups in the p53+/- or p53+/+ mice, although the high dose of FK228 increased the p21WAF1 mRNA expression in urinary bladder cancers in animals of both genotypes.
CONCLUSION
The present data indicate a lack of any inhibitory effects of FK228 on BBN-induced mouse urinary bladder carcinogenesis under the present conditions.
背景
FK228是一种组蛋白脱乙酰酶抑制剂，目前正处于癌症治疗的早期临床试验阶段，本研究检测了其对N-丁基-N-(4-羟丁基)-亚硝胺（BBN）诱导的小鼠膀胱癌发生的疗效。
材料与方法
在给予0.05%BBN处理10周后，对杂合子p53缺陷（p53+/-）和野生型（p53+/+）小鼠分别腹腔注射FK228（0、0.01和0.1mg/kg，每周3次），并分别在开始给药后的22周和24周处死小鼠。
结果
在p53+/-或p53+/+小鼠中，各剂量组之间膀胱肿瘤的发生率无显著差异，尽管高剂量的FK228增加了两种基因型动物膀胱癌中p21WAF1 mRNA的表达。
结论
目前的数据表明，在当前条件下，FK228对BBN诱导的小鼠膀胱癌发生没有任何抑制作用。
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