细胞分化帮助剂提高低浓度As_2O_3对肝癌细胞凋亡作用的体外实验  

Promoting effects of low-concentration arxenic trioxide with cell differential agentⅡon apoptosis of HCC cells in vitro

作　　者：沈雁[1] 刘建伟[1] 唐毅[1] 钟灿灿[1] 潘姝[1] 

机构地区：[1]广州市红十字会医院,广东省510220

出　　处：《中华肝胆外科杂志》2006年第6期393-396,共4页Chinese Journal of Hepatobiliary Surgery

基　　金：广东省科委广东省重点科技攻关科研基金(粤科计字1998110)

摘　　要：目的研究细胞分化帮助剂(CDA-Ⅱ)促进低浓度三氧化二砷(As_2O_3)对肝癌细胞株HepG-2,BEL-7402凋亡的协同效应。方法用四甲基偶氮唑蓝(MTT)法检测单用 CDA-Ⅱ或As_2O_3和联用对肝癌细胞株 HepG-2,BEL-7402生长及抑制率的影响:用乳酸脱氧酶(LDH)法检测药物对细胞膜的毒性反应;流式细胞仪(FCM)分析细胞周期和凋亡率变化。结果单用 CDA-Ⅱ和As_2O_3分别为3.0mg/ml 和50μmol/L 时,肝癌细胞株 BEL-7402,HepG-2发生凋亡达到最大值,而联用5μmol/L As_2O_3+1mg/ml CDA-Ⅱ可达到同样效果;结果显示:该浓度下 HepG_2的抑制率可达88%;BEL-7402的抑制率在100%;LDH 检测表明联用比单用 As_2O_310μmol/L 更安全。流式细胞仪结果显示凋亡率联合组为40.2%,明显高于单用组 As_2O_3(11.3%)或 CDA-Ⅱ(8.7%)。结论细胞分化帮助剂1mg/ml CDA-Ⅱ联用5μmol/L As_2O_3可促进肝癌细胞株 HepG-2,BEL-7402凋亡,可以明显降低 As_2O_3的使用浓度,减少对正常细胞的毒副作用。二者联用具有协同作用。Objective To investigate the possible promoting effects of arxenic trioxide （AS2O3 ） with cell differential agent Ⅱ （CDA-Ⅱ ） on apoptosis of HCC cells （HepG-2, BEL-7402）. Methods After AS2O3 or CDA- Ⅱ or both were added to the HCC cells, the proliferation and inhibition rates were determined with MTT. The toxic reaction of the 2 agents to cell membrane was detected by LDH. Cell cycle and apoptosis of the HCC cells were examined with flow cytometry. Results The HCC cells were inhibited with 3. 0 mg/ml CDA-Ⅱ or 50μmol/L As2O3 and maximal apoptotic rate appeared. The same effect could be achieved when 5 μmol/L As2O3 was used along with 1 mg/ml CDA-Ⅱ. The combined use was safer than As2O3 alone. Meanwhile, the apoptotic rate of HCC cells was significantly increased by combined use of the 2 agents as compared with using them alone （40. 2% vs. 11.3% and 8. 7%）. Conclusions CDA- Ⅱ has synergistic effects with As2O3 on promotion of apoptosis of HCC cells. Furthermore, the concentration of As2O3 can be decreased by combined use to reduce its toxic effect on normal cells.

关 键 词：癌 肝细胞 凋亡 三氧化二砷 细胞分化 

分 类 号：R735.7[医药卫生—肿瘤]