姜黄素对大鼠膀胱肿瘤的预防与治疗作用

Preventive and therapeutic effects of curcumin on bladder cancer in rats

目的:建立以N-甲基-N-亚硝基脲(N-methyl-N-nitrosourea,MNU)诱发膀胱癌的Wistar大鼠模型,研究姜黄素对诱发膀胱癌的化学干预作用,并探讨其可能的作用机制。方法:采用膀胱灌注MNU(1.5 mg/次)的方法诱发Wistar大鼠膀胱肿瘤(MNU灌注时间为第0、2、4、6和8周);实验分为2组,在诱癌的同时(第1、3、5、7和9周时,预防组)或者诱癌成功后(第10、12、14、16和18周时,治疗组)予以膀胱灌注姜黄素溶液(160 μmol/L)0.2 mL/只;分别在第13周时处死预防组大鼠,第23周时处死治疗组大鼠,获得的膀胱组织行苏木精-伊红(hematoxylin-eosin,HE)染色观察病理变化,Hoechst 33258荧光染色法检测肿瘤组织中细胞的凋亡情况。结果:在预防组中,第13周时姜黄素处理组膀胱癌的发生率为23.1%(3/13),其中浅表性癌3例,无肿瘤侵犯肌层;对照组肿瘤的发生率为66.7%(8/12),浅表性癌6例,肿瘤侵犯肌层2例,与对照组相比肿瘤的发生率、分期之间差异均有统计学意义。治疗组病理检测结果显示,肿瘤发生后再用姜黄素处理不能降低肿瘤分期,但能显著增加膀胱肿瘤细胞的凋亡。结论:姜黄素可抑制膀胱灌注MNU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;但对于已经成瘤的大鼠膀胱癌无明显疗效。

Objective：To establish N-methyl-N-nitrosourea（MNU）-induced bladder cancer model in Wistar rats,and to investigate the preventive and therapeutic effects of curcumin on bladder cancer,as well as to explore its potential mechanism.Methods：The bladder cancer in Wistar rats was induced by intravesical infusion of 1.5 mg MNU at 0,2,4,6 and 8 weeks.The rats were divided into two groups,including the preventive group [receiving 0.2 mL curcumin（160 μmol/L） at 1,3,5,7 and 9 weeks] and the therapeutic group [receiving 0.2 mL curcumin（160 μmol/L） at 10,12,14,16 and 18 weeks].The rats in the preventive group and the therapeutic group were sacrificed at 13 weeks and 23 weeks,respectively.The bladder cancer tissues were stained with hematoxylin and eosin（HE） for pathological examination.The apoptosis of tumor cells in the bladder cancer tissues was detected by fluorescence staining.Results：In the preventive group,three rats developed bladder cancer at 13 weeks（23.1%,3/13）,and the muscle invasion of superficial transitional cell carcinoma of bladder（TCC） was not observed.In the vehicle control group,the incidence of bladder cancer was 66.7%（8/12）.Six rats had superficial TCC,and two rats had TCC with muscle invasion.There were significant differences in the incidence and histologic staging of bladder cancer between the preventive group and the vehicle control group.The pathological results of the preventive group revealed that curcumin could not decrease the histologic stage of the developed cancer,but evidently increase the apoptosis rate of bladder cancer cells.Conclusion：Curcumin can effectively inhibit the tumorigenicity and progression of rat bladder cancer induced by MNU,and this mechanism may be related to apoptosis of tumor cells,but it has no effect on the developed bladder cancer.