Gartanin induces cell cycle arrest and autophagy and suppresses migration involving PI3K/Akt/mTOR and MAPK signalling pathway in human glioma cells.
Gartanin induces cell cycle arrest and autophagy and suppresses migration involving PI3K/Akt/mTOR and MAPK signalling pathway in human glioma cells.
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Gartanin 诱导细胞周期停滞和自噬，并抑制人胶质瘤细胞中涉及 PI3K/Akt/mTOR 和 MAPK 信号通路的迁移
DOI：
10.1111/jcmm.12937
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发表时间：
2017-01
影响因子：
5.3
通讯作者：
Liu A
中科院分区：
文献类型：
--
作者：
Luo M;Liu Q;He M;Yu Z;Pi R;Li M;Yang X;Wang S;Liu A
在中枢神经系统，神经胶质瘤是最常见的原发性脑肿瘤。弥漫性迁移和快速增殖是治疗成功的主要障碍。Gartanin是山竹中的一种天然山酮，在T98G胶质瘤细胞中以时间和浓度依赖的方式抑制增殖、迁移和集落形成，但在小鼠正常神经元HT22细胞中没有。低微摩尔时，Gartanin导致细胞周期阻滞在G1期，G1细胞周期调节蛋白cyclin D1的表达水平受到抑制，而cyclin依赖性激酶抑制剂p27Kip1的表达水平升高。此外，gartamin显著抑制了T98G胶质瘤细胞基质金属蛋白酶2/9 （MMP‐2/‐9）的分泌和活性，这可能与T98G胶质瘤细胞中丝裂原活化蛋白激酶（MAPK）信号通路的调节有关。此外，gartanin显著诱导T98G细胞自噬，增加GFP‐LC3点荧光，同时增加Beclin 1和LC3‐II的表达水平，抑制p62的表达水平。Gartanin处理导致PI3K/Akt/mTOR信号通路明显抑制，该信号通路在调节自噬中起重要作用。值得注意的是，自噬抑制剂包括3‐甲基腺嘌呤（3‐MA）和氯喹（CQ）显著地消除了gartanin介导的抗活力。这些结果表明，gartinin在T98G细胞中的抗增殖作用可能是通过自噬调节的细胞周期阻滞，这是由PI3K/Akt/mTOR信号通路调节的，而抗迁移作用可能是通过抑制MAPK信号通路中参与的MMP‐2/‐9活性来实现的。
In central nervous system, glioma is the most common primary brain tumour. The diffuse migration and rapid proliferation are main obstacles for successful treatment. Gartanin, a natural xanthone of mangosteen, suppressed proliferation, migration and colony formation in a time‐ and concentration‐dependent manner in T98G glioma cells but not in mouse normal neuronal HT22 cells. Gartanin, at low micromole, led to cell cycle arrest in G1 phase accompanied by inhibited expression level of G1 cell cycle regulatory proteins cyclin D1, while increased expression level of cyclin‐dependent kinase inhibitor p27Kip1. In addition, the secretion and activity of matrix metalloproteinases 2/9 (MMP‐2/‐9) were significantly suppressed in T98G cells treated with gartanin, and it might result from modulating mitogen‐activated protein kinases (MAPK) signalling pathway in T98G glioma cells. Moreover, gartanin significantly induced autophagy in T98G cells and increased GFP‐LC3 punctate fluorescence accompanied by the increased expression level of Beclin 1 and LC3‐II, while suppressed expression level of p62. Gartanin treatment resulted in obvious inhibition of PI3K/Akt/mTOR signalling pathway, which is important in modulating autophagy. Notably, gartanin‐mediated anti‐viability was significantly abrogated by autophagy inhibitors including 3‐methyladenine (3‐MA) and chloroquine (CQ). These results indicate that anti‐proliferation effect of gartanin in T98G cells is most likely via cell cycle arrest modulated by autophagy, which is regulated by PI3K/Akt/mTOR signalling pathway, while anti‐migration effect is most likely via suppression of MMP‐2/‐9 activity which is involved in MAPK signalling pathway.
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影响因子：
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作者：
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通讯作者：
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