p38MAPK在结肠癌细胞凋亡中的作用及与COX-2的关系  

Role of p38MAPK in Apoptosis of Colon Cancer Cells and Its Relationship with COX-2

作　　者：宋伟庆[1] 刘玉[2] 韦金英[2] 周保军[1] 韩彩丽[2] 陈怡[2] 

机构地区：[1]河北医科大学第二医院胃肠外科,050017 [2]河北医科大学病理教研室

出　　处：《肿瘤防治研究》2007年第5期359-362,共4页Cancer Research on Prevention and Treatment

摘　　要：目的探讨结肠癌细胞p38MAPK介导celecoxib(COX-2选择性抑制剂)抗肿瘤的作用及与COX-2的关系。方法用MTT法检测celecoxib对人结肠癌HT-29细胞生长的作用,用Western blot法测定各组细胞COX-2和Phosph-p38MAPK蛋白表达量,采用流式细胞术检测celecoxib和SB203580(p38MAPK特异性抑制剂)作用后HT-29细胞凋亡和细胞周期分布。结果p38MAPK和COX-2蛋白表达量与对照组(0.23±0.12)(0.95±0.14)相比,celecoxib可使p38MAPK蛋白表达水平明显升高(0.62±0.11),而使COX-2蛋白表达水平降低(0.44±0.11);SB203580使p38MAPK(0.12±0.05)及COX-2蛋白(0.23±0.13)表达水平均降低;SB203580和celecoxib共同作用后,p38MAPK表达量介于celecoxib和SB203580作用之间(0.43±0.12),COX-2表达量下降最为显著(0.15±0.10)。celecoxib和celecoxib+SB203580均可显著诱导HT-29细胞凋亡(P<0.01和P<0.05),与对照组(4.31%)相比,其凋亡率分别为40.95%、26.24%。结论在HT-29细胞中,celecoxib可通过活化p38MAPK而诱导结肠癌细胞凋亡,p38MAPK是COX-2的上游激酶,COX-2的表达水平受p38MAPK调控,并且COX-2可能对p38MAPK有负反馈调节作用。celecoxib是通过COX-2及其以外的p38MAPK通路诱导肿瘤细胞凋亡而发挥抗肿瘤作用的。Objective To investigate the role of p38MAPK in mediating celecoxib （COX 2 selective inhibitor） inhibited the growth of tumor in colon cancer cells and its relationship COX-2. Methods The cell gowth activity of HT-29 cells after the treatment by celecoxib was observed by MTT assay, flow cytome try was used to observed the effect of celecoxib and SB203580（p38MAPK specific inhibitor ） on apoptosis and the cell cycle distribution of HT-29 cells, the expression of Phosph p38MAPK and COX-2 protein was detected by Western blot. Results Compared with the expression of p38MAPK （0. 23 ± 0. 12）and COX-2（0. 95 ± 0. 14） of control group, p38MAPK expression （0. 62 ± 0. 11 ） was higher than control group, while the expression of COX-2（0. 44±0. 11 ）was lower than control group which was treated by eelecoxib. SB203580 could decrease the expression of p38MAPK（0. 12 ± 0. 05）and COX-2（0. 23 ± 0.13） ; the expression of p38MAPK（0. 43 ＋- 0. 12）was lower than control group, which was between celecoxib and SB203580, the decrease of COX-2 was most significant（0. 15 ± 0. 10）. Compared with the apoptosis of control group（4. 31%）, celecoxib and celecoxib ＋ SB203580 induced apoptosis significantly（P〈0. 01 and P〈0. 05）, the apoptosis rate of them was 40. 95% ,26. 24% respectively. Conclusion Celecoxib can induced the apoptosis of human colon cancer HT-29 cell lines, which may through the activation of p38MAPK. In signal transduction of HT-29 cell lines, the upstream kinase of COX2 is p38MAPK, the expression of COX-2 was regulation by p38MAPK, which has the effect of degenerative feedback regulation by COX-2. Celecoxib induced the apoptosis of tumor cells and play the role of anti-neoplasiasm through COX-2 and p38MAPK.

关 键 词：结肠癌细胞株 COX-2 P38MAPK 信号转导 凋亡 

分 类 号：R735.35[医药卫生—肿瘤]