Effect of peroxisome proliferators-activated receptor -? in the mechanisms of sulindac against large intestine carcinoma / 北京大学学报(医学版)

ABSTRACT

Objective: To compare effects of sulindac, PPAR? activator and PPAR? 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 PPAR?. Methods: Cell strain HT-29 of colonic cancer was divided into six groups the control group, sulindac group, 15d-PGJ2 (PPAR? activator) group, GW9662 (PPAR? 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. Conclusion: Both sulindac and PPAR? activator can inhibit proliferation and promote apoptosis of colonic cancer cells, and their effects can be antagonized by PPAR? antagonist, which indicates that as a kind of PPAR? ligand, sulindac can inhibit proliferation of colonic cancer cells via activating PPAR?.