Aloperine induces apoptosis and inhibits invasion in MG-63 and U2OS human osteosarcoma cells
Aloperine induces apoptosis and inhibits invasion in MG-63 and U2OS human osteosarcoma cells
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DOI：
10.1016/j.biopha.2017.09.066
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发表时间：
2018-01-01
影响因子：
7.5
通讯作者：
Gao, Weiyang
中科院分区：
文献类型：
--
作者：
Chen, Shao;Jin, Zhicheng;Gao, Weiyang
Aloperine （ALO）是从苦参中提取的一种新型生物碱类药物，具有抗炎、抗过敏、抗肿瘤和抗病毒等作用。在我们的研究中，我们评估了ALO对MG-63和U2OS骨肉瘤（OS）细胞的作用及其潜在机制。通过CCK-8和克隆生存试验观察到，ALO以剂量和时间依赖性的方式抑制了两种细胞系的增殖和克隆性。形态学变化、DAPI检测和流式细胞术数据显示，ALO诱导OS细胞凋亡，western blotting和qRT-PCR结果显示，ALO上调Bax和cleaved caspase-3蛋白及其mRNA，下调Bcl-2。此外，transwell侵袭实验显示，ALO对MG-63和U2OS细胞的侵袭有抑制作用。MMP-2和MMP-9的蛋白表达和mRNA表达均降低。ALO还下调了PI3K和p-AKT1的蛋白和mRNA表达。综上所述，ALO诱导MG-63和U2OS细胞凋亡并抑制侵袭可能通过抑制PI3K/AKT信号通路实现。
Aloperine (ALO) is a novel type of alkaloid drug that is extracted from S. alopecuroide, and exert an anti-inflammatory, anti-allergenic, antitumor and antiviral effects. In our study, we evaluated the effects and underlying mechanisms of ALO on MG-63 and U2OS osteosarcoma (OS) cells. ALO suppressed the proliferation and clonogenecity of both cell lines in a dose-and time-dependent manner as observed by CCK-8 and clonogenic survival assays. Data of morphologic changes, DAPI assays and flow cytometry showed that ALO induced apoptosis of OS cells, and the results of western blotting and qRT-PCR indicated that ALO upregulated protein and mRNA of Bax and cleaved caspase-3, while downregulated Bcl-2. Besides, ALO inhibited the invasion of MG-63 and U2OS cells as shown by transwell invasion assay. The protein and mRNA of MMP-2 and MMP-9 were decreased with ALO treatment. ALO also downregulated the protein and mRNA expression of PI3K and p-AKT1. In conclusion, ALO induced apoptosis and inhibited invasion in MG-63 and U2OS cells, which maybe through suppression of PI3K/AKT signaling pathway.