Arsenic Trioxide Inhibits Cholangiocarcinoma Cell Growth and induces Apoptosis
Arsenic Trioxide Inhibits Cholangiocarcinoma Cell Growth and induces Apoptosis
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DOI：
10.1007/s12253-009-9234-1
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发表时间：
2010-09-01
影响因子：
2.8
通讯作者：
Wu, Xiangyuan
中科院分区：
文献类型：
--
作者：
Zhong, Fei;Zhang, Shineng;Wu, Xiangyuan
三氧化二砷（As_2O_3）是中药中的一种有效成分，因其对多种肿瘤（包括实体瘤）的治疗作用而受到广泛关注。然而，As_2O_3对胆管癌的影响尚未见报道。在本研究中，我们首次证明，临床上可获得的浓度的As 2 O3抑制细胞生长，并诱导人胆管癌SK-ChA-1细胞凋亡。As 2 O3诱导的细胞凋亡可被caspase抑制剂部分抑制，并伴有Bcl-2家族蛋白表达的变化、线粒体膜电位（MMP）降低、线粒体细胞色素C释放、caspase-3、caspase-9激活以及聚（ADP-核糖）聚合酶（PARP）切割。因此，As 2 O3诱导SK-ChA-1细胞凋亡，通过caspase介导的，依赖的途径。As_2O_3抑制Akt磷酸化可能参与了As_2O_3介导的胆管癌细胞生长抑制和凋亡诱导。
Arsenic trioxide (As2O3), an ingredient in many traditional Chinese medicines, has drawn broad attention due to its therapeutic effects on a variety of cancers, including some solid tumors. However, the effects of As2O3 on cholangiocarcinoma have not been reported. In the present study, we demonstrate for the first time that clinically obtainable concentrations of As2O3 inhibit cell growth and induce apoptosis in human cholangiocarcinoma SK-ChA-1 cells. As2O3-induced apoptosis was partially inhibited by caspase inhibitor and accompanied by changes in the expression of Bcl-2 family proteins, decrease of mitochondrial membrane potential (MMP), release of cytochrome C from mitochondria, activation of caspase-3, caspase-9, and cleavage of poly (ADP-ribose) polymerase (PARP). Thus As2O3 induces apoptosis in SK-ChA-1 cells via mitochondria-mediated, caspases-dependent pathways. As2O3 inhibition of Akt phosphorylation may contribute to As2O3-mediated cholangiocarcinoma cell growth inhibition and apoptosis induction.