三氧化二砷和尿多酸肽抗肝癌作用的协同效应  

Antitumor effect of arsenic trioxide in combination with uroacitides on hepatoc ellular carcinoma

作　　者：刘建伟[1] 唐毅[2] 沈雁[2] 钟灿灿[2] 钟雪云[3] 

机构地区：[1]暨南大学附属广州红十字会医院普外科,510220 [2]暨南大学附属广州红十字会医院细胞实验室,510220 [3]暨南大学医学院病理科

出　　处：《中华普通外科杂志》2003年第2期114-116,共3页Chinese Journal of General Surgery

基　　金：广东省科委广东省重点科技攻关项目 (粤科计字1998110 )

摘　　要：目的　探讨三氧化二砷 (As2 O3)和尿多酸肽诱导肝癌细胞凋亡的协同效应。方法　不同浓度的As2 O3 和尿多酸肽处理肝癌细胞株 (BEL 740 2、HepG2 ) ,用四唑蓝比色法检测细胞存活率 ;活细胞荧光染色观测细胞凋亡及形态学变化、流式细胞术分析细胞周期变化及凋亡率。并将不同剂量用于肝癌荷癌裸鼠 ,观察两药对荷癌鼠的作用。结果　As2 O3 诱导肝癌细胞凋亡的敏感剂量是5 0 μmol L ,而与尿多酸肽共同应用的凋亡敏感剂量是 1 0 μmol LAs2 O3+1 0g L尿多酸肽。联合用药的实体型癌鼠皮下肿瘤生长的抑瘤率 40 44 % ,较单用三氧化二砷的抑瘤率 31 32 %提高了近 30 %。结论　尿多酸肽可增强As2 O3 诱导肝癌细胞的凋亡效应 ,两药具有协同作用。Objective To illustrate the possible sy nergistic effect of arsenic trioxide(Ａｓ ２Ｏ ３) and uroacitides on inductio n of apoptosis in hepatocellular carcinoma（HCC）. M ethods HCC cell lines BEL-7402 and Hep G 2 were trea ted with Ａｓ ２Ｏ ３ together with uroacitides for 4 successive days. Cell survi ving fraction was determined by MTT assay, morphological changes were observed b y immunofluorescence staining of Hoechst 33 258, cell cycle and the apoptosis in dex were determined by flow cytometry(FCM). Nude mouse bearing solid liver tumor was used in vivo experiments. Results With uroacitides added at the dosage of 1.0?g/L, apoptotic thres hold of Ａｓ ２Ｏ ３ on hepatoma cell lines was reduced from 5.0?μmol/L to 1.0?μmol/L (P<0.01). After the administration of Ａｓ ２Ｏ ３ and uro acitides, the growth of solid tumor were significantly inhibited, the combinatio n of two drugs led to much higher inhibitory rate, compared to separate usage of either drug alone. Conclusion Ｚ Uroacitides strongly potentiates Ａｓ ２Ｏ ３-induced apoptosis in hepat oma cells, and the two drugs produce a significant synergic effect.

关 键 词：三氧化二砷 肝肿瘤 砷剂 肽类 

分 类 号：R735.7[医药卫生—肿瘤]