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Role and mechanism of Sophoridine on proliferation inhibition in human glioma U87MG cell line

机译:槐定碱对人胶质瘤U87MG细胞增殖的抑制作用及其机制

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摘要

Sophoridine, a natural product obtained from medicinal plants, which has a variety of pharmacological effects, including anti-cancer effects, and selectively induces apoptotic cell death in a variety of human cancer cells in vitro and in vivo; however, its mechanism of action needs to be further elaborated. In this study, we investigated the effects of Sophoridine on the induction of apoptosis in human Glioma U87MG cells. Here, we found that Sophoridine can significantly inhibited cell proliferation, G2/M phase arrest, induced cell apoptosis and caused reactive oxygen species (ROS) generation and GSH content reduction. Sophoridine also triggered significant down-regulated the expression of p27, CDK2, Survivin, Livin, Bcl-2, E2F1 and the transcriptional activity of FoxM1, NF-κb and AP-1, meanwhile, up-regulated the expression of caspase-3/8, p53, Smac, c-JNK and p38-MAPK. Moreover, we found that Sophoridine significantly inhibited ubiquitin-proteasome in tumor cells. In conclusion, Sophoridine shows obvious anti-cancer activity on glioma cells by inducing cell apoptosis, inducing ROS accumulation, and activating mitochondrial signal pathways. Eventually, we believe Sophoridine could be used as a new drug for the treatment of glioma.
机译:槐定碱,一种从药用植物中获得的天然产物,具有多种药理作用,包括抗癌作用,并在体外和体内选择性诱导多种人癌细胞的凋亡。但是,其作用机制有待进一步阐述。在这项研究中,我们研究了槐定碱对人胶质瘤U87MG细胞凋亡的诱导作用。在这里,我们发现槐定碱可以显着抑制细胞增殖,G2 / M期停滞,诱导细胞凋亡并引起活性氧(ROS)生成和GSH含量降低。槐定碱还显着下调p27,CDK2,Survivin,Livin,Bcl-2,E2F1的表达以及FoxM1,NF-κb和AP-1的转录活性,同时上调caspase-3 / 8,p53,Smac,c-JNK和p38-MAPK。此外,我们发现槐定定显着抑制肿瘤细胞中的泛素-蛋白酶体。总之,槐定定通过诱导细胞凋亡,诱导ROS积累和激活线粒体信号通路,对神经胶质瘤细胞表现出明显的抗癌活性。最终,我们认为槐定碱可以用作治疗神经胶质瘤的新药。

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