【Animal modeling】-The chemical intervention effect and mechanism of curcumin on N-methylnitrosourea-induced bladder cancer in rats

  Objective: To analyze the chemical intervention effect and mechanism of curcumin on N-methylnitrosourea (MNU)-induced bladder cancer rat model.

  Methods: 100 SD rats were randomly divided into four groups, control group (10 rats), model group (10 rats), intervention group (40 rats) and treatment group (40 rats). The rats in the other three groups were perfused with MNU in the bladder to induce SD rats to form a bladder cancer model (the MNU solution with a concentration of 1 mg/mL was perfused into the bladder, and the MNU perfusion time was the second, fourth, and sixth time). and 8 weeks, 2 mg each time, once every 2 weeks, a total of 4 times), the model group was injected with distilled water when the rat bladder cancer was induced, and the intervention group was injected with curcumin solution (400 μmol/L) when the bladder was injected with MNU. , namely intravesical instillation at 1st, 3rd, 5th, 7th and 9th week, and euthanize the rats at 10th week; in the treatment group, curcumin solution (400 μmol/L) was injected into the bladder after inducing the rat bladder cancer model, that is, at the 10th, 10th, The bladder was instilled continuously for 12, 14, 16, and 18 weeks, and the rats were sacrificed at the 19th week. The obtained bladder tissue was stained with hematoxylin-eosin (HE) in turn to observe the pathological changes; TUNEL terminal labeling method was used to determine the tumor. Apoptosis in tissues; Western blot was used to detect the expression of apoptosis-related proteins.

  Results: The incidence rate of bladder cancer in the model group was 90% (9/10) at the 10th week, the incidence rate of bladder cancer in the intervention group was 12.5% (5/40) at the 10th week, and the incidence rate of the treatment group at the 10th week was 12.5% (5/40). The incidence of bladder cancer was 92.5% (37/40) at 2 weeks, and there was a significant difference in the incidence of bladder cancer between the intervention group and the model group (P<0.05), indicating that curcumin has an effect on MUN-induced bladder cancer in rats. Obvious chemical intervention effect; curcumin treatment was given after the formation of bladder cancer in the treatment group, the incidence of bladder cancer was 78.4% (30/37) in the 19th week, compared with the 10th week before treatment, it shows that curcumin has a therapeutic effect on bladder cancer can delay the progression of bladder cancer. TUNEL experiment confirmed that curcumin significantly promoted the apoptosis of bladder cancer cells and inhibited the proliferation of bladder cancer cells. Western blot results showed that curcumin inhibited the activation of NF-κB and effectively down-regulated the expression of NF-κB-regulated gene products.

  Conclusion: Curcumin has obvious chemical intervention effect on MNU-induced bladder cancer rat model, and the mechanism of action may be through inhibiting the activation of NF-κB and effectively down-regulating the gene products regulated by NF-κB to regulate the related factors in bladder cancer. The mechanism of protein expression, namely inhibiting proliferation, inducing apoptosis, further exerting anti-cancer chemical intervention effect and preventing the recurrence of bladder cancer.