体外过氧化物酶体增殖物激活受体-γ在舒林酸抗大肠肿瘤机制中的作用  

Effect of peroxisome proliferators-activated receptor -γ in the mechanisms of sulindac against large intestine carcinoma

作　　者：李传凤[1] 吕愈敏[1] 倪菊华[2] 李军[1] 

机构地区：[1]北京大学第三医院消化科,北京100083 [2]北京大学基础医学院生物化学与分子生物学系

出　　处：《北京大学学报（医学版）》2007年第1期72-76,共5页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金(30370633)资助~~

摘　　要：目的:对比观察舒林酸、过氧化物酶体增殖物激活受体-γ(peroxisomeproliferators-activatedreceptor-gam-ma,PPARγ)激动剂和PPARγ拮抗剂对结肠癌细胞增殖和凋亡的影响,初步探讨舒林酸抑制大肠肿瘤是否通过PPARγ起作用。方法:根据所加药物将结肠癌细胞株HT-29分为6组:舒林酸组,15-去氧-△12,14-前列腺素J2(15-deoxy-△12,14-prostaglandinJ2,15d-PGJ2,PPARγ激动剂)组,GW9662(PPARγ拮抗剂)组,舒林酸+GW9662组,15d-PGJ2+GW9662组及空白对照组,培养24和48h后,进行增殖细胞核抗原(proliferationcellnuclearantigen,PCNA)的免疫细胞化学染色测定各组细胞增殖情况;并收集各组细胞,用流式细胞仪AnnexinV-FITC/PI双染法测定各组细胞的凋亡。结果:(1)各组结肠癌细胞增殖情况:加药24和48h后PCNA表达的阳性率,对照组为33.2%±4.5%及25.0%±4.7%;舒林酸组为11.8%±3.7%及8.6%±1.9%;15d-PGJ2组为11.2%±2.5%及11.4%±2.1%;GW9662组为35.3%±4.3%及26.8%±3.9%;舒林酸+GW9662组为16.5%±5.3%及12.2%±2.4%;15d-PGJ2+GW9662组为21.0%±4.8%及21.5%±4.2%。(2)各组结肠癌细胞凋亡率:加药24h后各组细胞凋亡率,对照组为13.0%±1.0%;舒林酸组为41.0%±2.6%;15d-PGJ2组为11.5%±0.6%;GW9662组为12.4%±0.9%;舒林酸+GW9662组为33.6%±2.3%;15d-PGJ2+GW9662组为13.0%±1.0%。加药48h后各组细胞凋亡率,对照组为14.0%±3.4%;舒林酸组为95.3%±1.5%;15d-PGJ2组为31.5%±2.3%;GW9662组为13.0±1.9%;舒林酸+GW9662组为86.8%±0.4%;15d-PGJ2+GW9662组为12.9%±1.0%。结论:舒林酸与PPARγ激动剂作用相似,均可以抑制结肠癌细胞的增殖和促进结肠癌细胞的凋亡,二者作用均可被PPARγ的拮抗剂所拮抗,说明舒林酸作为PPARγ配体,其抑制结肠癌细胞增殖和促进结肠癌细胞凋亡的作用可能与激活PPARγ有关。Objective： To compare effects of sulindac, PPARγ activator and PPARγ/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 PPARγ Methods： Cell strain HT-29 of colonic cancer was divided into six groups： the control group, sulindac group, 15d-PGJ2 （PPARγ activator） group, GW9662 （PPARγ 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 ceil apoptosis status was determined by double staining method of AnnexinVFITC/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% and26.8% ±3.9% of GW9662 group, 16.5% ± 5.3% and 12.2 % ±2.4% ofsulindac ＋ 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% s0.6% of 15d-PGJ2 group, 12.4% s0.9% 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 PPARγ activator can inhibit proliferation and promote apoptosis of colonic cancer cells, and their effects can be antagonized by PPARγ/antagonist, which indicates that as a kind

关 键 词：过氧化物酶 舒林酸 结肠肿瘤 

分 类 号：R735.35[医药卫生—肿瘤]