丝裂霉素诱导胆管癌细胞凋亡过程中p38MAPK表达的研究  

A study on p38MAPK activity during mitomycin-induced apoptosis of cholangiocarcinoma cell lines

作　　者：王博[1] 祝学光[1] 李军[1] 赵华[1] 赵娜[1] 

机构地区：[1]北京大学人民医院普外科,100044

出　　处：《中华普通外科杂志》2004年第2期111-113,共3页Chinese Journal of General Surgery

摘　　要：目的研究丝裂霉素诱导胆管癌细胞凋亡过程中p38MAPK表达的变化 ,探讨p38MAPK在其中的作用。方法用AnnexinV PI染色及流式细胞技术分析丝裂霉素及p38MAPK抑制剂SB2 0 35 80对胆管癌细胞凋亡的影响 ,同时利用Westernblot法测定经丝裂霉素及SB2 0 35 80处理人胆管癌RBE细胞后 ,p38MAPK及其下游ATF 2 (反映p38MAPK激酶活性 )的表达水平。结果丝裂霉素诱导RBE细胞凋亡率为 (8 91± 0 83) % (P <0 0 1) ,同时p38MAPK和ATF 2 (p38MAPK下游基因 ,反映其激酶活性 )表达显著升高 (P <0 0 1)。用SB2 0 35 80阻断p38MAPK通路后 ,丝裂霉素诱导凋亡的作用进一步加强 ,凋亡率达 (2 2 2± 2 6 ) % (P <0 0 1)。结论丝裂霉素可以活化p38MAPK通路 ,p38MAPK可能起到保护胆管癌RBE细胞逃避丝裂霉素诱导的凋亡 ,阻断该通路可增强丝裂霉素诱导胆管癌细胞凋亡的作用。Objective To observe the expression of p38MAPK activity during mitomycin-induced cell cycle arrest of cholangiocarcinoma. Using p38MAPK inhibitor SB203580 to analyze the effect on chemotherapy of cholangiocarcinoma. Methods The selected human cholangicarcinoma cell lines RBE was treated with mitomycin or together with SB203580, cell apoptosis was analysed by AnnexinV-FITC and propidium iodide(PI)double staining and flow cytometry (FCM), p38 and ATF-2 activity was detected by Western blot. Results Mitomycin induced apoptosis of RBE cell line, the ratio of apoptosis was (8.91±0.83)%( P < 0.01). Mitomycin together with SB203580 enhanced the apoptosis of RBE cell line to the ratio of (22.19± 2.57)%( P <0.01). The level of p38 and ATF-2 activity increased rapidly at 30 min. Conclusions Mitomycin activates p38MAPK, p38MAPK protected RBE cells from apoptosis induced by mitomycin, the blockade of p38 could inhance mitomycin-induced apoptosis.

关 键 词：丝裂霉素 胆管癌 细胞凋亡 P38MAPK 流式细胞术 P38MAPK抑制剂 

分 类 号：R735.8[医药卫生—肿瘤]