Regulation of the cell cycle and PI3K/Akt/mTOR signaling pathway by tanshinone I in human breast cancer cell lines.
Regulation of the cell cycle and PI3K/Akt/mTOR signaling pathway by tanshinone I in human breast cancer cell lines.
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细胞周期和PI3K/AKT/MTOR信号传导途径在人类乳腺癌细胞系中的调节。
DOI：
10.3892/mmr.2014.2819
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发表时间：
2015-02
影响因子：
3.4
通讯作者：
Tang J
中科院分区：
文献类型：
--
作者：
Wang L;Wu J;Lu J;Ma R;Sun D;Tang J
乳腺癌是全球女性癌症相关死亡的第二大原因。因此，确定对抗该疾病死亡率的替代策略非常重要。本研究的目的是探讨丹参酮I（Tan I）对雌激素反应性MCF - 7和雌激素非依赖性MDA - MB - 453人乳腺癌细胞致瘤性的影响。采用细胞计数试剂盒 - 8（Cell Counting Kit - 8）检测Tan I的细胞毒性，利用流式细胞术检测细胞凋亡和细胞周期分布，并使用荧光显微镜观察细胞形态。此外，使用特异性蛋白抗体通过蛋白质印迹分析检测参与磷脂酰肌醇 - 3 - 激酶（PI3K）/蛋白激酶B（Akt）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路的细胞周期调节蛋白和凋亡相关蛋白。无论对雌激素是否有反应，MCF - 7和MDA - MB - 453细胞对Tan I同样敏感。Tan I具有相似的抗增殖活性并诱导细胞凋亡，导致S期阻滞，同时伴有细胞周期蛋白B减少以及细胞周期蛋白E和细胞周期蛋白A蛋白增加，这可能与细胞周期蛋白依赖性激酶抑制剂p21Cip1和p27Kip1的上调有关。此外，发现Tan I可下调PI3K/Akt/mTOR信号通路中的抗凋亡成分并上调相关的凋亡成分。值得注意的是，使用PI3K抑制剂LY294002处理可降低磷酸化（p）-PI3K、p - Akt和p - mTOR的水平。这些结果清楚地表明，Tan I的作用机制至少部分涉及对PI3K/Akt/mTOR信号通路的影响，为抗癌药物的设计和开发提供了新的信息。
Breast cancer is the second leading cause of cancer-related mortality in females worldwide. Therefore, identifying alternative strategies to combat the disease mortality is important. The aim of the present study was to investigate the effect of tanshinone I (Tan I) on the tumorigenicity of estrogen-responsive MCF-7 and estrogen-independent MDA-MB-453 human breast cancer cells. The cytotoxicity of Tan I was evaluated using a Cell Counting Kit-8 assay, the apoptosis and cell cycle distribution were detected using flow cytometry and the cell morphology was observed using a fluorescence microscope. In addition, the cell cycle regulatory proteins and apoptosis-associated proteins involved in the phosphatidylinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway were detected using western blot analysis using specific protein antibodies. The MCF-7 and MDA-MB-453 cells were equally sensitive to Tan I regardless of their responsiveness to estrogen. Tan I exerted similar antiproliferative activities and induction of apoptosis, resulting in S phase arrest accompanied by decreases in cyclin B and increases in cyclin E and cyclin A proteins, which may have been associated with the upregulation of cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1. In addition, Tan I was found to downregulate anti-apoptotic and upregulate associated apoptotic components of the PI3K/Akt/mTOR signaling pathway. Notably, treatment with the PI3K inhibitor, LY294002, decreased the levels of phosphorylated (p)-PI3K, p-Akt and p-mTOR. These results clearly indicated that the mechanism of action of Tan I involved, at least partially, an effect on the PI3K/Akt/mTOR signaling pathway, providing new information for anticancer drug design and development.
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影响因子：
4.6
作者：
Li, Yanli;Gong, Yi;Li, Linglin;Abdolmaleky, Hamid M.;Zhou, Jin-Rong
通讯作者：
Zhou, Jin-Rong
DOI：
10.3980/j.issn.2222-3959.2012.06.05
发表时间：
2012-12-18
影响因子：
1.4
作者：
Cai, Na;Dai, Shun-Dong;Chen, Lei
通讯作者：
Chen, Lei
PKB/Akt 通过电离辐射后上调 Mre11 表达促进癌细胞中的 DSB 修复
影响因子：
8
作者：
Deng, R.;Tang, J.;Zhu, X-F
通讯作者：
Zhu, X-F
影响因子：
3.5
作者：
Mandal, D;Moitra, PK;Basu, J
通讯作者：
Basu, J
影响因子：
4.3
作者：
Lee, W. Y. W.;Chiu, L. C. M.;Yeung, J. H. K.
通讯作者：
Yeung, J. H. K.