单酰基甘油脂肪酶抑制剂JZL184对结直肠癌细胞系凋亡的影响及其机制  

Effect of monoacylglycerol lipase inhibitor JZL184 on apoptosis of colorectal cancer cells

作　　者：马牧原[1] 白洁[1] 常伟龙[1] 陶凯雄[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院胃肠外科Ⅱ,湖北省武汉市430022

出　　处：《世界华人消化杂志》2015年第14期2256-2263,共8页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.81172294~~

摘　　要：目的:研究JZL184对结直肠癌细胞系细胞凋亡的影响及其可能的机制.方法:分别用JZL184,JZL184联合不同浓度5-氟尿嘧啶(5-fluorouracil,5-Fu)及单用5-Fu干预SW480和Lovo 48 h,流式细胞仪检测结直肠癌细胞系SW480和Lovo细胞凋亡率变化.Western blot检测JZL184干预SW480及Lovo 48 h后p-AKT、p-m TOR、proCaspase3和pro-Caspase8蛋白水平的变化.结果:在结直肠癌细胞系SW480及Lovo中,J Z L184联合5-F u与单用5-F u组相比细胞凋亡不同程度增加(在SW480中凋亡率提升分别为:JZL184+500μmol/L 5-Fu 13.91%±9.13%,JZL184+200μmol/L 5-Fu 26.34%±13.32%,JZL184+100μmol/L 5-Fu 43.32%±8.04%,JZL184+10μmol/L 5-Fu 31.4%±5.82%;在L o v o中凋亡率提升分别为:JZL184+500μmol/L 5-Fu 17.56%±8.14%,JZL184+200μmol/L 5-Fu 33.04%±9.49%,JZL184+100μmol/L 5-Fu 36.91%±16.63%,JZL184+10μmol/L 5-Fu 21.26%±11.03%.与对照组相比,10μmol/L JZL184可不同程度抑制结直肠癌细胞系SW480及Lovo p-A K T、p-m T O R、p r o-C a s p a s e3、p r oCaspase8蛋白水平(P<0.05).结论:JZL184抑制AKT-m TOR通路及促进p r o-C a s p a s e8和p r o-C a s p a s e3裂解活化从而增强5-Fu诱导结直肠癌细胞系SW480,L o v o细胞凋亡,提高结直肠癌细胞系对5-Fu敏感性.AIM： To investigate whether JZL184, a monoacylglycerol lipase inhibitor, induces apoptosisof colorectal cancer cells and to explore the possible mechanism.METHODS： SW480 and Lovo cells were treated with JZL184, JZL184 ＋ 5-fluorouracil（5-Fu） or 5-Fu alone for 48 h. Apoptosis was assessed by flow cytometry. The protein levels of p-AKT, p-mTOR, pro-Caspase3 and proCaspase8 were assessed by Western blot.RESULTS： Treatment with JZL184 ＋ 5-Fu increased SW480 and Lovo cell apoptosis more significantly than 5-Fu alone（apoptosis increase in SW480 cells： JZL184 ＋ 500 μmol/L5-Fu 13.91% ± 9.13%, JZL184 ＋ 200 μmol/L 5-Fu26.34% ± 13.32%, JZL184 ＋ 100 μmol 5-Fu 43.32%± 8.04%, JZL184 ＋ 10 μmol 5-Fu 31.4% ± 5.82%;Lovo cells： JZL184 ＋ 500 μmol/L 5-Fu 17.56% ±8.14%, JZL184 ＋ 200 μmol/L 5-Fu 33.04% ± 9.49%,JZL184 ＋ 100 μmol/L 5-Fu 36.91% ± 16.63%,JZL184 ＋ 10 μmol/L 5-Fu 21.26% ± 11.03%）.Treatment with JZL184 significantly decreased the protein levels of p-AKT, p-mTOR, proCaspase3 and pro-Caspase8 in colorectal cancer SW480 and Lovo cells（P〈0.05）.CONCLUSION： JZL184 can inhibit the AKTmTOR pathway and promote pro-Caspase8 and pro-Caspase3 activation to increase the apoptosis of SW480 and Lovo cells treated with 5-Fu.

关 键 词：单酰基甘油脂肪酶 JZL184 结直肠癌 AKT-m TOR CASPASE8 CASPASE3 

分 类 号：R735.34[医药卫生—肿瘤]