AIM To investigate the chemopreventive effect of sulindac, one of the nonstroidal anti inflammatory drugs (NSAIDs), on the growth of N methyl N nitrosourea (MNU) induced mouse colonic tumors.
AIM: To study the effect of sulindac on colon cancer induction in mice. METHODS: The chemo-preventive action of 80 ppm sulindac fed during initiation and post-initiation and 100 ppm sulindac fed during progressive sta...AIM: To study the effect of sulindac on colon cancer induction in mice. METHODS: The chemo-preventive action of 80 ppm sulindac fed during initiation and post-initiation and 100 ppm sulindac fed during progressive stages of induction of colon carcinogenesis in mice was investigated using 1,2-dimethylhydrazine (DMH). Using the terminal deoxynudeobdyl transferase-mediated dUTP nick-end labeling (TUNEL) technique and PCNA immunohistochemical staining, we observed the apoptotic and proliferative cell density changes at different carcinogenic stages and the effect of sulindac on these two phenomena. RESULTS: Dietary sulindac significantly inhibited the incidence of colonic neoplasmas in mice. Compared with the control group, feeding sulindac during initiation and post-initiation stages inhibited the incidence by 46.7-50.4%, and feeding sulindac during progressive stages inhibited the incidence by 41.1%. Animals that were fed sulindac showed less serious pathological changes than those that were fed the control diet (P<0.01, H=33.35). There was no difference in the density of proliferating cells among those groups which were or were not fed sulindac. In the same period, feeding sulindac resulted in a higher density of apoptotic cells than feeding control diet. CONCLUSION: Sulindac has an anti-carcinogenic function in mice. Its effect on preventing colon carcinogenesis is better than its effect on treating established tumors. By inducing apoptosis, sulindac inhibited the development of colon cancer and delayed canceration. Sulindac has no effect on proliferation. The anti-carcinogenic properties of sulindac are most effective in the moderate and severe stages of dysplasia and canceration.展开更多
Objective To investigate the effects of sulindac metabolites on proliferation and apoptosis in the human umbilical vein endothelial cell line ECV304 in vitro Methods The proliferation profile of ECV304 was dete...Objective To investigate the effects of sulindac metabolites on proliferation and apoptosis in the human umbilical vein endothelial cell line ECV304 in vitro Methods The proliferation profile of ECV304 was determined by methyl thiazolyl tetrazolium (MTT) method Cell cycle distribution, apoptosis and the ultrastructure of ECV304 were detected by flow cytometry (FCM) and electron microscopy, respectively Results MTT assay showed that the sulfide inhibited the proliferation of ECV304 and its effect was dose dependent; the IC 50 was 200 μmol/L FCM showed that the sulfide changed cell cycle distribution The cell cycle distribution was as follows: G 1 phase (control group 77 74%±1 58%; sulfone group 75 63%±2 12%; sulfide group 46 12%±1 60%); S phase (control group 13 64%±1 22%; sulfone group 16 40±2 30%; sulfide group 27 26%±2 08%); G 2 M phase (control group 8 61%±0 67%; sulfone group 7 98%±0 49%; sulfide group 26 62%±3 54%) The apoptosis rates in the control group, sulfone group and sulfide group were 6 08%±3 39%, 4 81%±2 14% and 51 90%±5 67%, respectively Sulfide reduced the proportion of G 1 phase, increased the proportion of S phase, G 2 M phase and the apoptosis rate significantly ( P <0 01, vs control) In the sulfide treated cells, there were nuclear fragmentation and chromosomal condensation, shrinkage of the cell and loss of contact with neighboring cells Apoptotic bodies were observed Sulfone showed no effect on cell proliferation, cell cycle distribution or cell morphology Conclusions Sulfide can significantly reduce the proliferation of ECV304, change the cell cycle distribution and arrest cells in G 2 M phase where apoptosis may be induced Sulfone has no such effects on this cell line展开更多
文摘AIM To investigate the chemopreventive effect of sulindac, one of the nonstroidal anti inflammatory drugs (NSAIDs), on the growth of N methyl N nitrosourea (MNU) induced mouse colonic tumors.
基金Supported by the Natural Science Foundation of Tianjin, No. 973611311
文摘AIM: To study the effect of sulindac on colon cancer induction in mice. METHODS: The chemo-preventive action of 80 ppm sulindac fed during initiation and post-initiation and 100 ppm sulindac fed during progressive stages of induction of colon carcinogenesis in mice was investigated using 1,2-dimethylhydrazine (DMH). Using the terminal deoxynudeobdyl transferase-mediated dUTP nick-end labeling (TUNEL) technique and PCNA immunohistochemical staining, we observed the apoptotic and proliferative cell density changes at different carcinogenic stages and the effect of sulindac on these two phenomena. RESULTS: Dietary sulindac significantly inhibited the incidence of colonic neoplasmas in mice. Compared with the control group, feeding sulindac during initiation and post-initiation stages inhibited the incidence by 46.7-50.4%, and feeding sulindac during progressive stages inhibited the incidence by 41.1%. Animals that were fed sulindac showed less serious pathological changes than those that were fed the control diet (P<0.01, H=33.35). There was no difference in the density of proliferating cells among those groups which were or were not fed sulindac. In the same period, feeding sulindac resulted in a higher density of apoptotic cells than feeding control diet. CONCLUSION: Sulindac has an anti-carcinogenic function in mice. Its effect on preventing colon carcinogenesis is better than its effect on treating established tumors. By inducing apoptosis, sulindac inhibited the development of colon cancer and delayed canceration. Sulindac has no effect on proliferation. The anti-carcinogenic properties of sulindac are most effective in the moderate and severe stages of dysplasia and canceration.
文摘Objective To investigate the effects of sulindac metabolites on proliferation and apoptosis in the human umbilical vein endothelial cell line ECV304 in vitro Methods The proliferation profile of ECV304 was determined by methyl thiazolyl tetrazolium (MTT) method Cell cycle distribution, apoptosis and the ultrastructure of ECV304 were detected by flow cytometry (FCM) and electron microscopy, respectively Results MTT assay showed that the sulfide inhibited the proliferation of ECV304 and its effect was dose dependent; the IC 50 was 200 μmol/L FCM showed that the sulfide changed cell cycle distribution The cell cycle distribution was as follows: G 1 phase (control group 77 74%±1 58%; sulfone group 75 63%±2 12%; sulfide group 46 12%±1 60%); S phase (control group 13 64%±1 22%; sulfone group 16 40±2 30%; sulfide group 27 26%±2 08%); G 2 M phase (control group 8 61%±0 67%; sulfone group 7 98%±0 49%; sulfide group 26 62%±3 54%) The apoptosis rates in the control group, sulfone group and sulfide group were 6 08%±3 39%, 4 81%±2 14% and 51 90%±5 67%, respectively Sulfide reduced the proportion of G 1 phase, increased the proportion of S phase, G 2 M phase and the apoptosis rate significantly ( P <0 01, vs control) In the sulfide treated cells, there were nuclear fragmentation and chromosomal condensation, shrinkage of the cell and loss of contact with neighboring cells Apoptotic bodies were observed Sulfone showed no effect on cell proliferation, cell cycle distribution or cell morphology Conclusions Sulfide can significantly reduce the proliferation of ECV304, change the cell cycle distribution and arrest cells in G 2 M phase where apoptosis may be induced Sulfone has no such effects on this cell line
