ABSTRACT
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 re-ceived 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 exami-nation 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 de-lay 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 activa-tion 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 inhibi-tion 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 an-ti-cancer intervention and prevention of bladder cancer recurrence.
ABSTRACT
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 re-ceived 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 exami-nation 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 de-lay 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 activa-tion 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 inhibi-tion 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 an-ti-cancer intervention and prevention of bladder cancer recurrence.
ABSTRACT
Objective To investigate the effect of bacillus Calmette-Guérin(BCG)on bladder cancer cells and their metabolites, and to preliminarily explore the possible mechanisms of BCG in the treatment of bladder cancer. Methods The rat model of bladder cancer was induced by intravesical instillation with N-methylnitrosourea(MNU). Bladder cancer cells and normal transitional epithelial cells were isolated and primarily cultured, and were divided into 5 groups according to the different components of the culture medium. The concentration of tumor necrosis factor-α(TNF-α) and interleukin-10(IL-10)in the supernatant of each group was detected by enzyme linked immunosorbent assay (ELISA). The concentration of BCG to inhibit the cancer cell growth was determined by MTT assay. Apoptosis of bladder cancer cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL). Results Among the 15 rats,2 rats died after 2 times of instillation, and 3 rats died after 3 times of instillation, without obvious tumors found at autopsy. The other 10 rats were killed after completion of the intravesically instillation of MNU, and obvious tumors were found in 8 of them after dissection. The results of MTT assay showed that BCG had an inhibitory effect on the growth of bladder cancer cells,and the inhibitory rate was positively correlated with the concentration of BCG. The results of ELISA showed that the concentrations of TNF-α in the supernatant of groups B and D were(160.654 ± 5.775) ng/L and(124.443 ± 4.972)ng/L, respectively, with significant differences from those of the other three groups. The concentrations of IL-10 in the groups B and E were(16.973 ± 3.428)ng/L and(20.327 ± 2.721)ng/L, significantly higher than those of the other three groups. Apoptosis of cancer cells was not found in all groups. HE staining of the primary bladder cancer cells showed that the volume of cell nucleus was increased, and the nucleo-cytoplasmic ratio was increased. The number of nucleoli in some cells was increased and some nuclei appeared like ink drops with prominent nucleoli. Conclusions BCG has an inhibitory effect on the growth of rat bladder cancer cells. IL-10 and TNF-α secreted by the tumor cells might be involved in this regulatory process. However,apoptosis does not show an obvious effect on this inhibitory process.