AICAR induces mitochondrial apoptosis in human osteosarcoma cells through an AMPK-dependent pathway.
AICAR induces mitochondrial apoptosis in human osteosarcoma cells through an AMPK-dependent pathway.
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AICAR通过AMPK依赖性途径诱导人骨肉瘤细胞线粒体凋亡
DOI：
10.3892/ijo.2016.3775
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发表时间：
2017-01
影响因子：
5.2
通讯作者：
Akisue T
中科院分区：
文献类型：
--
作者：
Morishita M;Kawamoto T;Hara H;Onishi Y;Ueha T;Minoda M;Katayama E;Takemori T;Fukase N;Kurosaka M;Kuroda R;Akisue T
amp活化蛋白激酶（AMPK）激活剂5-氨基咪唑-4-羧酰胺核糖核苷酸（AICAR）调节细胞能量代谢，促进线粒体增殖和凋亡。以往的研究表明，AICAR在多种癌症中具有抗癌作用，但AMPK和/或AICAR在骨肉瘤中的作用尚未见报道。在本研究中，我们在体外和体内研究了AICAR对人骨肉瘤肿瘤生长和线粒体凋亡的影响。体外实验采用AICAR处理MG63和KHOS两种人骨肉瘤细胞系，通过WST、TUNEL染色和免疫印迹分析评估AICAR对细胞生长和线粒体凋亡的影响。在体内，用AICAR治疗患有人骨肉瘤的小鼠，评估治疗后肿瘤的线粒体增殖和凋亡活性。体外实验表明，AICAR在两种骨肉瘤细胞系中均能激活AMPK，抑制细胞生长，诱导线粒体凋亡。在体内，AICAR显著降低骨肉瘤生长，但没有明显的体重减轻，AICAR增加了治疗后肿瘤组织的线粒体增殖和凋亡活性。AICAR通过ampk依赖性过氧化物酶体增殖体激活受体-γ共激活因子-1α (PGC-1α)/线粒体转录因子A (TFAM)/线粒体途径在骨肉瘤细胞中显示出抗癌作用。本研究结果强烈提示AICAR可被认为是治疗人骨肉瘤的有效药物。
The AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) modulates cellular energy metabolism, and promotes mitochondrial proliferation and apoptosis. Previous studies have shown that AICAR has anticancer effects in various cancers, however the roles of AMPK and/or the effects of AICAR on osteosarcoma have not been reported. In the present study, we evaluated the effects of AICAR on tumor growth and mitochondrial apoptosis in human osteosarcoma both in vitro and in vivo. For in vitro experiments, two human osteosarcoma cell lines, MG63 and KHOS, were treated with AICAR, and the effects of AICAR on cell growth and mitochondrial apoptosis were assessed by WST assays, TUNEL staining, and immunoblot analyses. In vivo, human osteosarcoma-bearing mice were treated with AICAR, and the mitochondrial proliferation and apoptotic activity in treated tumors were assessed. In vitro experiments revealed that AICAR activated AMPK, inhibited cell growth, and induced mitochondrial apoptosis in both osteosarcoma cell lines. In vivo, AICAR significantly reduced osteosarcoma growth without apparent body weight loss and AICAR increased both mitochondrial proliferation and apoptotic activity in treated tumor tissues. AICAR showed anticancer effects in osteosarcoma cells through an AMPK-dependent peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α)/mitochondrial transcription factor A (TFAM)/mitochondrial pathway. The findings in this study strongly suggest that AICAR could be considered as a potent therapeutic agent for the treatment of human osteosarcoma.
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影响因子：
3.7
作者：
Fu X;Wan S;Lyu YL;Liu LF;Qi H
通讯作者：
Qi H
影响因子：
64.5
作者：
Narkar VA;Downes M;Yu RT;Embler E;Wang YX;Banayo E;Mihaylova MM;Nelson MC;Zou Y;Juguilon H;Kang H;Shaw RJ;Evans RM
通讯作者：
Evans RM
影响因子：
4.8
作者：
El-Mir, MY;Nogueira, V;Leverve, X
通讯作者：
Leverve, X
DOI：
10.1073/pnas.0705070104
发表时间：
2007-07-17
影响因子：
11.1
作者：
Jaeger, Sibylle;Handschin, Christoph;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
影响因子：
3.5
作者：
Ekstrand, MI;Falkenberg, M;Larsson, NG
通讯作者：
Larsson, NG