漆黄素对大鼠膀胱癌的预防作用及其机制研究  

Preventive effects of fisetin on bladder cancer in rats and its mechanisms

作　　者：李晶[1] 武敏[1] 屈卫星[1] 程永毅[1] 余义[1] 邹铁军[1] 姜亚卓[1] 赵华才[1] 

机构地区：[1]陕西省人民医院泌尿外科,陕西西安710068

出　　处：《现代肿瘤医学》2014年第7期1514-1519,共6页Journal of Modern Oncology

基　　金：陕西省自然科学基金资助项目(编号:2013JQ4013)

摘　　要：目的:建立以N-甲基-N-亚硝基脲(N-methyl-N-nitrosourea,MNU)诱发的Wistar大鼠膀胱癌模型,研究漆黄素对大鼠膀胱癌的预防作用及其作用机制。方法:采用膀胱灌注MNU的方法诱发Wistar大鼠原位膀胱肿瘤(MNU灌注时间为第2、4、6和8周)。第1周至18周行漆黄素溶液(400μmol/L)膀胱灌注。在第19周时处死大鼠,获得的膀胱组织行苏木精-伊红(HE)染色观察病理变化。TUNEL末端标记法测定肿瘤组织中细胞凋亡情况。Western blot检测凋亡相关蛋白表达。结果:第19周时漆黄素处理组膀胱癌的发生率为22.2%(4/18),MNU诱癌组肿瘤的发生率为70.6%(12/17),两组相比肿瘤的发生率、分期之间差异均有统计学意义。TUNEL实验证实漆黄素显著增加膀胱肿瘤细胞的凋亡。Western blot结果发现,漆黄素上调促凋亡分子p53和Bax蛋白表达,下调抗凋亡分子Bcl-2和Survivin表达。结论:漆黄素可抑制MNU膀胱灌注诱导的大鼠膀胱癌的发生与进展,其机制可能与诱导膀胱肿瘤细胞凋亡有关。Objective：To establish N methyl N nitrosourea （MNU） induced bladder cancer model in Wist ar rats, and to investigate the preventive effects of fisetin on bladder cancer, as well as to explore its potential mecha nism. Methods ：The bladder cancer in Wistar rats was induced by intravesical infusion of 1.5 mg MNU at 2,4,6 and 8 weeks and intravesicalFisetin （400μmol/L） from 1 week to 18 weeks. The rats were sacrificed at the 19th week. The bladder cancer tissues were stained with hematoxylin and eosln （HE） for pathological examination. The apoptosis of tumor cells in the bladder cancer tissues was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling. The apoptosis related protein was detected by Western blot. Results： At week 19, the tumor occurrence was 22.2% （4/ 18 ） in fisetin treatment group and 70.6% （12/17） in MNU induced group. There were significant differences in the incidence and histologic staging of bladder cancer between two groups. The pathological resuhs revealed that fisetin could decrease the histologic stage of the developed cancer. Fisetin treatment evidently increased the apoptosis rate of bladder cancer cells by TUNEL. Western blot results showed that fisetin increased expression of pro ap0ptotic mole cule p53 and Bax and meanwhile decreased the expression of anti apoptotic molecule Bcl 2 and Survivin. Conclu sion ： Fisetin can effectively inhibit the tumorigenicity and progression of rat bladder cancer induced by MNU, and the mechanism may be related to apoptosis of tumor cells.

关 键 词：漆黄素 膀胱癌 凋亡 动物实验 N-甲基-N-亚硝基脲 

分 类 号：R737.14[医药卫生—肿瘤]