Sulindac induces apoptosis and protects against colon carcinoma in mice.
OBJECTIVE
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 deoxynucleotidyl 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.


CONCLUSIONS
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.
Sun
Bao-Cun
BC
Department of Pathology, Tianjin Medical University, Tianjin 300070, China. baocunsun@eyou.com
Zhao
Xiu-Lan
XL
Zhang
Shi-Wu
SW
Liu
Yi-Xin
YX
Wang
Lan
L
Wang
Xin
X
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma / Q000473:pathology / Q000517:prevention & control*; D003110:Colonic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D004032:Diet; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013467:Sulindac / Q000008:administration & dosage / Q000494:pharmacology*
D000970:Antineoplastic Agents; D013467:Sulindac