Effect of arsenic trioxide on multidrug resistant hepatocellular carcinoma cells
Effect of arsenic trioxide on multidrug resistant hepatocellular carcinoma cells
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DOI：
10.1016/j.canlet.2005.05.017
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发表时间：
2006-05-18
期刊：
影响因子：
9.7
通讯作者：
Fung, Kwok-Pui
中科院分区：
文献类型：
--
作者：
Chan, Judy Yuet-Wa;Siu, Katy Pak-Yan;Fung, Kwok-Pui
我们前期的研究表明三氧化二砷（As_2O_3）通过诱导细胞凋亡抑制人肝癌细胞（HepG_2）的生长。本研究观察了三氧化二砷（As_2O_3）对多药耐药肝癌细胞（R-HepG_2）的作用。MTT法检测As 2 O3对R-HepG 2细胞增殖的抑制作用。用三氧化二砷处理后，进行DNA片段化和Annexin V-PI染色以诱导细胞凋亡。为研究三氧化二砷对P-糖蛋白的影响，采用免疫印迹法检测P-糖蛋白的表达变化。结果表明，As 2 O3能有效抑制R-HepG 2细胞增殖，并呈剂量和时间依赖性，其作用机制为诱导细胞凋亡，而不影响细胞周期。R-HepG 2细胞对As_2O_3的敏感性与亲本HepG 2细胞相似。Western分析表明，As_2O_3不能维持R-HepG_2细胞内P-糖蛋白的表达，可能不是P-糖蛋白结合和挤出的底物。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Our previous study showed that arsenic trioxide (As2O3) was effective in inhibiting the growth of human hepatocellular carcinoma (HepG2) cells via induction of apoptosis. In the present study, we examined the effect of As2O3 on multidrug resistant human hepatocellular carcinoma (R-HepG2) cells which are characterized with overexpression of mdr1 gene and P-glycoprotein. The anti-proliferation of R-HepG2 by As2O3 was examined by MTT assay. For the induction of apoptosis, DNA fragmentation and Annexin V-PI staining were performed after treatment with arsenic trioxide. To study the effect of arsenic trioxide on P-glycoprotein, Western analysis probing anti-P-glycoprotein antibody was used to monitor the change of its expression. Results showed that As2O3 was effective in inhibiting the cell proliferation of R-HepG2 cells in a dose- and time-dependent manner via induction of apoptosis without affecting the cell cycle. The sensitivity of R-HepG2 cells toward As2O3 was found to be similar to that of the parental HepG2 cells. The Western analysis showed that As2O3 was probably not the substrate to be bound and extruded by P-glycoprotein in R-HepG2 cells because it could not maintain the cellular P-glycoprotein expression. (c) 2005 Elsevier Ireland Ltd. All rights reserved.