雷公藤甲素及其脂质体对TFK-1细胞增殖和凋亡的影响  

The effect of triptolide and triptolide loaded liposomes on proliferation and apoptosis to TFK-1 cells

作　　者：杨锐 李红波[2] 王兵[2] 邹声泉[2] 

机构地区：[1]武汉市第五医院普外科,430050 [2]华中科技大学附属同济医院普外科,武汉430030

出　　处：《中华实验外科杂志》2014年第11期2378-2380,共3页Chinese Journal of Experimental Surgery

基　　金：国家科技部国际合作与交流项目（2010DFA31870）

摘　　要：目的 观察雷公藤甲素（TP）及其脂质体（TP-LP）对人胆管癌细胞株TFK-1增殖和凋亡的影响;比较两者在体内抑制肿瘤生长的作用,探讨脂质体作为TP纳米载体的可行性.方法 采用噻唑蓝（MTT）比色法、平板克隆形成实验、流式细胞术等观察不同浓度的TP及TP-LP对胆管癌细胞TFK-1增殖、周期和凋亡的影响.建立TFK-1细胞种植瘤模型,比较TP及TP-LP对裸鼠种植瘤生长的抑制作用.结果 TP及TP-LP均呈时间、剂量依赖性地抑制TFK-1的增殖,TP-LP对TFK-1的抑制作用优于TP（P ＜0.05）.TP和TP-LP均可阻滞TFK1细胞于G0/G1期,100 nmol/L浓度作用48 h后G0/G1期细胞比例分别为（73.26 ±2.56）％、（84.35±3.85）％,差异有统计学意义（P＜0.05）.两者均可以诱导TFK1细胞的凋亡,100 nmol/L浓度作用48 h后TFK1细胞凋亡的比例分别为（22.71±3.66）％、（35.23±4.02）％,差异有统计学意义（P＜ 0.05）;TFK1裸鼠种植瘤试验中,对照组、TP组和TP-LP组肿瘤体积分别为（1 073.33±20.82）、（306.67±15.28）、（88.0±8.26） mm^3,差异有统计学意义（P＜0.05）;用药21 d后处死裸鼠,对照组、TP组和TP-LP组荷瘤鼠体质量分别为（24.69±1.53）、（22.85±1.99）、（22.80±1.77）g,3组之间的差异无统计学意义（P＞0.05）.结论 TP和TP-LP在体外均能通过阻滞细胞周期和诱导细胞凋亡而抑制TFK-1细胞的增殖,TP-LP的作用强于TP;在体内两者均具有抑制种植瘤生长的作用,TP-LP的抑瘤作用强于TP;TP-LP抗肿瘤的作用强于TP单药,是一种有潜力的新型载药体系.Objective To research the effect of triptolide （TP） and triptolide loaded liposome （TP-LP） on proliferation and apoptosis to human cholangiocarcinoma cell line TFK-1,and the inhibition of tumor growth so that we can evaluate the feasibility of liposome as TP nano-carrier.Methods Detected the effect of TP and TP-LP at different concentration level on proliferation,cell cycle and apoptosis to TFK-1 by methyl thiazolyl tetrazolium （MTT）,clone formation assay and flow cytometry.In animal study,we constructed TFK-1 node mice xenograft mode to compare the inhibiting effect to mice xenograft of TP and TP-LP.Results TP and TP-LP inhibited proliferation of TFK-1 both time and dose dependent,and TP-LP was superior to TP （P 〈 0.05）.Both TP and TP-LP could block TFK-1 cells in G0/G1 phase and promote them to apoptosis.After treated by TP or TP-LP at 100nmol/L after 48 h,the percentage of G0/G1 phase were （73.26 ± 2.56） % and （84.35 ± 3.85） % seperately,and the percentage of apoptosis were （22.71 ± 3.66）% and （35.23 ± 4.02） % separately,both of which had significant difference （P 〈 0.05）.The volume of xenograft in control,TP and TP-LP group were （1 073.33 ± 20.82）,（306.67 ± 15.28） and （88.0 ±8.26） mm3 seperately,which had significant difference （P 〈0.05）.While 21 days after drug-using,the weight of mice in three groups were （24.69 ± 1.53）,（22.85 ± 1.99） and （22.80 ± 1.77） g separately,which had no significant difference （P 〉 0.05）.Conclusion Both of TP and TP-LP can inhibit proliferation of TFK-1 by blocking cell cycle and promoting apoptosis in vitro,and inhibit xenograft growth in vivo,while TP-LP is effective.So TP-LP is a potential new drug,which is more effective than TP.

关 键 词：雷公藤甲素 脂质体 增殖 凋亡 胆管癌 

分 类 号：R735.8[医药卫生—肿瘤]