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叶亭诱导人肺腺癌细胞细胞周期停滞和微管去稳定化的分子机制

Molecular Mechanisms Underlying Yatein-Induced Cell-Cycle Arrest and Microtubule Destabilization in Human Lung Adenocarcinoma Cells.

作者信息

Ho Shang-Tse, Lin Chi-Chen, Tung Yu-Tang, Wu Jyh-Horng

机构信息

Department of Forestry, National Chung Hsing University, Taichung 402, Taiwan.

Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan.

出版信息

Cancers (Basel). 2019 Sep 17;11(9):1384. doi: 10.3390/cancers11091384.

Abstract

Yatein is an antitumor agent isolated from Florin leaves extract. In our previous study, we found that yatein inhibited the growth of human lung adenocarcinoma A549 and CL1-5 cells by inducing intrinsic and extrinsic apoptotic pathways. To further uncover the effects and mechanisms of yatein-induced inhibition on A549 and CL1-5 cell growth, we evaluated yatein-mediated antitumor activity in vivo and the regulatory effects of yatein on cell-cycle progression and microtubule dynamics. Flow cytometry and western blotting revealed that yatein induces G/M arrest in A549 and CL1-5 cells. Yatein also destabilized microtubules and interfered with microtubule dynamics in the two cell lines. Furthermore, we evaluated the antitumor activity of yatein in vivo using a xenograft mouse model and found that yatein treatment altered cyclin B/Cdc2 complex expression and significantly inhibited tumor growth. Taken together, our results suggested that yatein effectively inhibited the growth of A549 and CL1-5 cells possibly by disrupting cell-cycle progression and microtubule dynamics.

摘要

叶亭是一种从弗洛林叶提取物中分离出的抗肿瘤剂。在我们之前的研究中,我们发现叶亭通过诱导内源性和外源性凋亡途径抑制人肺腺癌A549和CL1-5细胞的生长。为了进一步揭示叶亭诱导的抑制对A549和CL1-5细胞生长的影响及机制,我们评估了叶亭在体内介导的抗肿瘤活性以及叶亭对细胞周期进程和微管动力学的调节作用。流式细胞术和蛋白质免疫印迹法显示,叶亭诱导A549和CL1-5细胞发生G/M期阻滞。叶亭还使这两种细胞系中的微管不稳定并干扰微管动力学。此外,我们使用异种移植小鼠模型评估了叶亭在体内的抗肿瘤活性,发现叶亭处理改变了细胞周期蛋白B/细胞分裂周期蛋白2复合物的表达并显著抑制肿瘤生长。综上所述,我们的结果表明,叶亭可能通过破坏细胞周期进程和微管动力学有效抑制A549和CL1-5细胞的生长。

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