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苦参碱通过使Akt信号通路失活,在体外抑制骨肉瘤细胞生长并诱导其凋亡。

Matrine inhibits the growth and induces apoptosis of osteosarcoma cells in vitro by inactivating the Akt pathway.

作者信息

Xu Gong-Ping, Zhao Wei, Zhuang Jin-Peng, Zu Jia-Ning, Wang Duan-Yang, Han Fei, Zhang Zhi-Peng, Yan Jing-Long

机构信息

Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, 148 Baojian Road, Harbin, 150081, China.

出版信息

Tumour Biol. 2015 Mar;36(3):1653-9. doi: 10.1007/s13277-014-2764-5. Epub 2014 Nov 5.

Abstract

Matrine, a natural product, has been demonstrated to be a promising chemotherapeutic drug for some cancers. Using flow cytometric analysis of the cell cycle and apoptosis, we found that matrine inhibited the proliferation and induced apoptosis in the human osteosarcoma (OS) cell lines MG63, HOS, U2OS, and SAOS2 in vitro in a dose-dependent manner. We therefore assessed the role of the serine/threonine kinase Akt in the regulation of matrine-mediated cell growth inhibition and apoptosis induction in human OS cell lines. After treatment for 48 h, matrine induced G0/G1-stage cell cycle arrest in MG63, U2OS, and SAOS2 cells associated with an increase in the expression of p27(Kip1) and a decrease in the expression of Akt, glycogen synthase kinase 3 (GSK3)-β (Ser9), and cyclin D1. Furthermore, the pro-apoptotic factor Bax was upregulated. Overall, our findings suggest that matrine may be an effective anti-osteosarcoma drug due to its ability to inhibit proliferation and induce apoptosis in OS cells, possibly through the involvement of Akt signaling.

摘要

苦参碱是一种天然产物,已被证明是一种对某些癌症有前景的化疗药物。通过对细胞周期和凋亡进行流式细胞术分析,我们发现苦参碱在体外以剂量依赖的方式抑制人骨肉瘤(OS)细胞系MG63、HOS、U2OS和SAOS2的增殖并诱导其凋亡。因此,我们评估了丝氨酸/苏氨酸激酶Akt在调节苦参碱介导的人OS细胞系细胞生长抑制和凋亡诱导中的作用。处理48小时后,苦参碱诱导MG63、U2OS和SAOS2细胞发生G0/G1期细胞周期阻滞,这与p27(Kip1)表达增加以及Akt、糖原合酶激酶3(GSK3)-β(Ser9)和细胞周期蛋白D1表达降低有关。此外,促凋亡因子Bax上调。总体而言,我们的研究结果表明,苦参碱可能是一种有效的抗骨肉瘤药物,因为它能够抑制OS细胞的增殖并诱导其凋亡,可能是通过Akt信号通路介导的。

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