| Objective: To explore the mechanism of N-4-hydroxyphenyl retinamide (4-HPR)intervention during rat models with bladder cancer are induced by N-methyl-N-nitrosourea (MNU).Methods: Seventy SD rats were randomly divided into5groups, including controlgroup (A group, n=10), MNU model group (B group, n=15), MNU/4-HPR interventiongroup (C group, n=15), MNU/ADM intervention group (D group, n=15), andMNU/BCG (E group, n=15). All rats in the C, D and E groups were administrated withMNU (0.2mg) and corresponding drug interchangeably, including4-HPR (0.2mg),ADM (0.2mg) and BCG (0.5mg) by intravesical instillation for10weeks. A and Bgroups were perfused with saline and MNU (0.2mg) for5weeks, respectively. Thedrug remained in the bladder was not less than2h. After one week at the last perfusion,all rats were killed. The indexes were performed as follow: pathological examination ofbladder with H&E staining, immunohistochemical staining with S-P for detectingCOX-2expression and MVD count, and TUNEL method for testing apoptosis of cancercells.Results:1. Pathological examination of bladder tissue showed: the vast majority ofepithelial cells in A group was arranged in alignment, pathogenic changes were notdetected oberviously;the incidence of carcinogenesis was93.3%. The mainperformances were increased cell layers, disordered cell arrangements, pathological karyokinesis, as well as local or regional papillary hyperplasia in mucosa. Although thepathologic changes in C, D and E groups were similar to that in B group, the degrees ofcell layers and pathological karyokinesis in the three groups were less than that in Bgroup.2. The results from immunohistochemistry with S-P method showed: the expressedlevels of COX-2in C, D and E groups were1.70±1.892,1.67±1.936and1.50±1.780and lower than that in B group (4.80±3.293)(P <0.05). However, there has nosignificant difference among C, D and E groups (P>0.05).(2) The counts of MVD in C,D and E groups were19.10±4.228,16.89±2.205and13.20±2.974, respectively,which were lower than the count in B group (30.30±4.218). Statistical analysis showed,MVD count in C group has statistical significance, compared with that in B group(P <0.05), while MVD count in E group was significant lower than those in C and D groups(P <0.05). However, there was no statistically difference from the MVD countsbetween C and D groups (P>0.05).3. Apoptosis of cancer cells TUNEL test showed: apoptosis index of cancer cellsin C, D and E groups were (12.90±2.424)%,(14.89±2.759)%and (15.10±2.514)%, respectively, which were all higher than that in B group (3.50±1.581)%. Statistical analysis showed: apoptosis index of cancer cell in C group washigher than that in B group（P <0.05); however, there were no significant differences in the index of apoptosis of cancer cells among C, D and E groups (P>0.05).Conclusion:4-HPR is effective in the intervention of bladder cancer induced by MNU,which is similar to those of ADM and BCG. The mechanism intervened by4-HPR maybe based on inducing the apoptosis of cancer cell,and inhibiting COX-2expression andangiogenesis. |
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