Effect of curcumin on chemical intervention and mechanism of MNU-induced bladder cancer in rats
Received:May 10, 2017  
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KeyWord:Curcumin;N-methylnitrosourea;Bladder cancer;Chemical intervention;Mechanism of action;Rats
吴金生 青岛大学, 山东青岛市
王清明 潍坊医学院,山东潍坊市
郑传秋 潍坊医学院,山东潍坊市
纪萌 潍坊医学院,山东潍坊市
孙立江 青岛大学, 山东青岛市
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      Objective To study the effect of curcumin on rat model of N-methylnitrosourea (MNU)-induced bladder cancer and its mechanism. Methods One hundred SD rats were randomly divided into four groups:control group (n=10), model group (n=10), intervention group (n=40) and treatment group (n=40). Rats in the control group received intravesical infusion of distilled water. Rats in the other three groups were given MNU (1 mg/mL) in 2 mL saline at 2nd, 4th, 6th and 8th weeks to induce bladder cancer. In the model group, the rats were injected with distilled water in the bladder. The rats in the intervention group received 2 mL curcumin solution (400 μmol/L) at the 1st, 3rd, 5th, 7th and 9th weeks, and were sacrificed at the 11th week. In the model group, the rats were injected with distilled water in the bladder. In the treatment group, the rats had intravesical instillation of curcumin in the bladder (400 μmol/L, 2 mL) at 10, 12, 14, 16, and 18 weeks, and sacrificed at the 19th week. Bladder tissue samples were taken for pathological examination using hematoxylin and eosin (HE) staining. TUNEL staining assay was used to detect the apoptosis in tumor tissue. The expression of apoptosis-related proteins was detected by Western blot.Results The incidence of bladder cancer was 90% (9/10) in the model group, 12.5% (5/40) in the intervention group and 92.5% (37/40) in the treatment group at the 10th week, showing a significant difference between the intervention group and model group (P<0.05), indicating an obvious interventional effect of curcumin on the bladder cancer. The incidence rate of bladder cancer in the treatment group was 78.4% (30/37) at the 19th week, and compared with the 10th week before treatment, showing that curcumin can delay the recurrence of bladder cancer. TUNEL staining assay confirmed that curcumin significantly promoted the apoptosis in bladder cancer cells and inhibited their proliferation. The Western blot analysis showed that curcumin inhibited the activation of NF-κB and effectively down-regulated the expression of NF-κB-regulated gene product.Conclusions Curcumin has a significant interventional effect on MNU-induced bladder cancer in the rat models. The mechanism may be through inhibition of NF-κB activation and effective down-regulated NF-κB regulation of the gene products, and to regulate the expression of related proteins in bladder cancer, i.e., inhibition of proliferation, induction of apoptosis, and further play a role of anti-cancer intervention and prevention of bladder cancer recurrence.
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