[Effect of peroxisome proliferators-activated receptor-gamma in the mechanisms of sulindac against large intestine carcinoma].
OBJECTIVE
To compare effects of sulindac, PPARgamma activator and PPARgamma antagonist on the proliferation and apoptosis of the colonic cancer cells, and to investigate whether sulindac exerts its colonic neoplasm inhibiting activity through pathway of PPARgamma.


METHODS
Cell strain HT-29 of colonic cancer was divided into six groups: the control group, sulindac group, 15d-PGJ2 (PPARgamma activator) group, GW9662 (PPARgamma antagonist) group, sulindac+GW9662 group and 15d-PGJ2+ GW9662 group. After 24 and 48 hours' culturing, proliferation status of each group was determined by immunocytochemical staining of PCNA, and cell apoptosis status was determined by double staining method of AnnexinV-FITC/PI, examined on flow cytometer.


RESULTS
(1) Proliferation status of the colonic cancer cells of each group: 24 and 48 hours after medication, PCNA positive ratios were 33.2%+/- 4.5% and 25.0%+/-4.7% of the control group, 11.8%+/-3.7% and 8.6%+/-1.9% of sulindac group, 11.2%+/-2.5% and 11.4%+/-2.1% of 15d-PGJ2 group, 35.3%+/-4.3% and 26.8%+/-3.9% of GW9662 group, 16.5%+/-5.3% and 12.2 %+/-2.4% of sulindac + GW9662 group, 21.0%+/-4.8% and 21.5%+/-4.2% of 15d-PGJ2+GW9662 group. (2) Apoptosis ratio of colonic cancer cells of each group: 24 hours after medication, apoptosis rate of colonic cancer cells was 13.0%+/-1.0% of the control group, 41.0%+/-2.6% of sulindac group, 11.5%+/-0.6% of 15d-PGJ2 group, 12.4%+/-0.9% of GW9662 group,33.6%+/-2.3% of sulindac+GW9662 group, and 13.0%+/-1.0% of 15d-PGJ2 + GW9662 group. 48 hours after medication, apoptosis rate was 14.0%+/-3.4% of the control group, 95.3%+/-1.5% of sulindac group, 31.5%+/-2.3% of 15d-PGJ2 group, 13.0%+/-1.9% of GW9662 group, 86.8%+/-0.4% of sulindac+GW9662 group, and 12.9%+/-1.0% of 15d-PGJ2+GW9662 group.


CONCLUSIONS
Both sulindac and PPARgamma activator can inhibit proliferation and promote apoptosis of colonic cancer cells, and their effects can be antagonized by PPARgamma antagonist, which indicates that as a kind of PPARgamma ligand, sulindac can inhibit proliferation of colonic cancer cells via activating PPARgamma.
Li
Chuan-feng
CF
Department of Gastroenterology, Peking University Third Hospital, Beijing 100083, China.
Lv
Yu-min
YM
Ni
Ju-hua
JH
Li
Jun
J
D000813:Anilides / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D013467:Sulindac / Q000494:pharmacology*
C477819:15-deoxyprostaglandin J2; C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D000970:Antineoplastic Agents; D047495:PPAR gamma; D018809:Proliferating Cell Nuclear Antigen; D013467:Sulindac; D015230:Prostaglandin D2