Artesunate induces G2/M cell cycle arrest through autophagy induction in breast cancer cells
Artesunate induces G2/M cell cycle arrest through autophagy induction in breast cancer cells
复制标题
青蒿琥酯通过诱导乳腺癌细胞自噬诱导 G2/M 细胞周期停滞
DOI：
10.1097/cad.0000000000000089
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发表时间：
2014-07-01
影响因子：
2.3
通讯作者：
Tao, Min
中科院分区：
文献类型：
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作者：
Chen, Kai;Shou, Liu-Mei;Tao, Min
我们发现青蒿琥酯(ART)对MCF-7和MDA-MB-231乳腺癌细胞的生长有抑制作用。ART使细胞周期停滞于G2/M期，并伴随着p21的上调。ART上调了自噬(II型程序性细胞死亡)的启动者Beclin1的表达。此外，ART还刺激了Lc3的聚集，这被认为是自噬形成的标志。我们进一步证实了LC3从I型转变为II型。3-MA是一种经典的自噬抑制剂，它能减弱ART诱导的自噬小体形成、细胞生长抑制、G2/M期停滞和p21上调。自噬诱导和p21上调也被Beclin1基因敲除所抑制。此外，ART通过依赖自噬的级联反应使乳腺癌细胞对化疗药表阿霉素敏感。我们的研究表明，ART诱导乳腺癌细胞自噬，并表明ART的抗癌作用是通过自噬途径发挥的。此外，抗逆转录病毒药物能使乳腺癌细胞对表阿霉素化疗敏感。我们的结果为进一步开发ART作为一种治疗乳腺癌的新型治疗剂提供了基础。
We found that artesunate (ART) inhibited the growth of MCF-7 and MDA-MB-231 breast cancer cells. ART arrested the cell cycle in the G2/M phase, which was accompanied by an upregulation of p21. ART upregulated the expression of Beclin1, an initiator of autophagy (type II programmed cell death). In addition, ART stimulated the aggregation of LC3, which is considered to be a marker of autophagosome formation. We further verified the transformation of LC3 from type I into type II. 3-MA, a classical autophagy inhibitor, attenuated ART-induced autophagosome formation, cell growth repression, G2/M arrest, and p21 upregulation. Autophagy induction and p21 upregulation were also repressed by knockdown of Beclin1. Furthermore, ART sensitized breast cancer cells to the chemotherapeutic agent epirubicin through an autophagy-dependent cascade. Our study showed that ART induced autophagy in breast cancer cells and indicated that the anticancer effects of ART were exerted through an autophagy pathway. Moreover, ART sensitized breast cancer cells to epirubicin chemotherapy. Our results provide a basis for further development of ART as a novel therapeutic agent for the treatment of breast cancer.