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蟾毒灵诱导胆囊癌细胞的细胞周期停滞和凋亡。

Bufalin induces cell cycle arrest and apoptosis in gallbladder carcinoma cells.

作者信息

Jiang Lin, Zhao Ming-Ning, Liu Tian-Yu, Wu Xiang-Song, Weng Hao, Ding Qian, Shu Yi-Jun, Bao Run-Fa, Li Mao-Lan, Mu Jia-Sheng, Wu Wen-Guang, Ding Qi-Chen, Cao Yang, Hu Yun-Ping, Shen Bai-Yong, Tan Zhu-Jun, Liu Ying-Bin

机构信息

Institute of Biliary Tract Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai, China,

出版信息

Tumour Biol. 2014 Nov;35(11):10931-41. doi: 10.1007/s13277-014-1911-3. Epub 2014 Aug 2.

Abstract

Bufalin, a major digoxin-like immunoreactive component of the Chinese medicine Chan Su, has been shown to exert a potential for anticancer activity against various human cancer cell lines in vitro. However, no detailed studies have so far been reported on its action on human gallbladder carcinoma cells. In this study, bufalin remarkably inhibited growth in human gallbladder cancer cells by decreasing cell proliferation, inducing cell cycle arrest and apoptosis in a dose-dependent manner. Bufalin also disrupted the mitochondrial membrane potential (ΔΨm) and regulated the expression of cell cycle and apoptosis regulatory molecules. Activation of caspase-9 and the subsequent activation of caspase-3 indicated that bufalin may be inducing mitochondria apoptosis pathways. Intraperitoneal injection of bufalin for 3 weeks significantly inhibited the growth of gallbladder carcinoma (GBC-SD) xenografts in athymic nude mice. Taken together, the results indicate that bufalin may be a potential agent for the treatment of gallbladder cancer.

摘要

蟾毒灵是中药蟾酥中一种主要的类地高辛免疫反应性成分,已显示出在体外对多种人类癌细胞系具有抗癌活性的潜力。然而,迄今为止尚未有关于其对人胆囊癌细胞作用的详细研究报道。在本研究中,蟾毒灵通过以剂量依赖的方式降低细胞增殖、诱导细胞周期停滞和凋亡,显著抑制人胆囊癌细胞的生长。蟾毒灵还破坏线粒体膜电位(ΔΨm)并调节细胞周期和凋亡调节分子的表达。半胱天冬酶-9的激活以及随后半胱天冬酶-3的激活表明蟾毒灵可能诱导线粒体凋亡途径。腹腔注射蟾毒灵3周可显著抑制无胸腺裸鼠胆囊癌(GBC-SD)异种移植物的生长。综上所述,结果表明蟾毒灵可能是一种治疗胆囊癌的潜在药物。

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