Anti-tumor effects of Atractylenolide I on bladder cancer cells.
Anti-tumor effects of Atractylenolide I on bladder cancer cells.
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白术内酯I对膀胱癌细胞的抗肿瘤作用
DOI：
10.1186/s13046-016-0312-4
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发表时间：
2016-03-01
期刊：
影响因子：
--
通讯作者：
Ma Q
中科院分区：
文献类型：
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作者：
Yu R;Yu BX;Chen JF;Lv XY;Yan ZJ;Cheng Y;Ma Q
白术皂苷I（ATR-1）是白术的活性成分，对多种肿瘤具有细胞毒作用。然而，ATR-1对膀胱癌的作用知之甚少。在本研究中，ATR-1的抗肿瘤活性在体内和体外的膀胱癌细胞进行了检查。MTT法检测ATR-1的细胞毒作用。流式细胞仪检测细胞周期分布和凋亡水平。Western blotting检测细胞凋亡、细胞周期及PI 3 K/Akt/mTOR信号通路相关蛋白的表达。裸鼠皮下注射T-24和253 J人膀胱癌细胞建立肿瘤模型。ATR-1通过上调p21蛋白表达，下调cyclin B1、CDK 1和Cdc 25 c蛋白表达，抑制膀胱癌细胞增殖，使细胞周期阻滞于G2/M期。同时，ATR-1还通过激活线粒体凋亡途径而引发细胞凋亡。机制研究表明，ATR-1的抗肿瘤作用还依赖于对PI 3 K/Akt/mTOR信号通路的抑制。最后，小鼠研究显示ATR-1阻断T-24或253 J诱导的异种移植肿瘤生长而没有明显的毒性。ATR-1有可能成为治疗膀胱癌的潜在药物。
Atractylenolide I (ATR-1), an active component of Rhizoma Atractylodis Macrocephalae, possesses cytotoxicity against various carcinomas. However, little is known about the effects of ATR-1on bladder cancer. In the present study, the anti-tumor activity of ATR-1 was examined on bladder cancer cells both in vivo and in vitro. MTT assay was used to assess the cytotoxic effect of ATR-1. Cell cycle distribution and apoptosis levels were evaluated using flow cytometry. Western blotting assay was applied to measure the levels of proteins associated with the apoptotic pathway, cell cycle progression and PI3K/Akt/mTOR signaling pathway. Tumor models in nude mice were induced by injection of T-24 and 253J human bladder cancer cells. ATR-1 inhibited bladder cancer cell proliferation, arrested cell cycle in G2/M phase through up-regulation of p21 and down-regulation of cyclin B1, CDK1 and Cdc25c. Meanwhile, ATR-1 also triggered cellular apoptosis depending on the activation of mitochondrial apoptotic pathway. Mechanism investigation indicated that ATR-1 exerts its anti-tumor effect also relies on the inhibition of PI3K/Akt/mTOR signaling pathway. Finally, mice studies showed that ATR-1 blocked the T-24 or 253J-induced xenograft tumor growth without noticeable toxicity. ATR-1 may be served as a potential therapeutic agent for the treatment of bladder cancer.