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原花青素 B2 通过抑制 PI3K/AKT 通路抑制骨肉瘤细胞增殖并诱导其凋亡。

Proanthocyanidin B2 inhibits proliferation and induces apoptosis of osteosarcoma cells by suppressing the PI3K/AKT pathway.

机构信息

Department of Orthopedics, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, China.

出版信息

J Cell Mol Med. 2020 Oct;24(20):11960-11971. doi: 10.1111/jcmm.15818. Epub 2020 Sep 10.

Abstract

Osteosarcoma (OS) is the most common primary malignant bone tumour in children and adolescents. The long-term survival rate of OS patients is stubbornly low mainly due to the chemotherapy resistance. We therefore aimed to investigate the antitumoral effects and underlying mechanisms of proanthocyanidin B2 (PB2) on OS cells in the current study. The effect of PB2 on the proliferation and apoptosis of OS cell lines was assessed by CCK-8, colony formation, and flow cytometry assays. The target gene and protein expression levels were measured by qRT-PCR and Western blotting. A xenograft mouse model was established to assess the effects of PB2 on OS proliferation and apoptosis in vivo. Results from in vitro experiments showed that PB2 inhibited the proliferation and induced apoptosis of OS cells, and also increased the expression levels of apoptosis-related proteins. Moreover, PB2 induced OS cell apoptosis through suppressing the PI3K/AKT signalling pathway. The in vivo experiments further confirmed that PB2 could inhibit OS tumour growth and induce its apoptosis. Taken together, these results suggested that PB2 inhibited the proliferation and induced apoptosis of OS cells through the suppression of the PI3K/AKT signalling pathway.

摘要

骨肉瘤(OS)是儿童和青少年中最常见的原发性恶性骨肿瘤。OS 患者的长期生存率一直很低,主要是由于化疗耐药。因此,本研究旨在探讨原花青素 B2(PB2)对 OS 细胞的抗肿瘤作用及其潜在机制。通过 CCK-8、集落形成和流式细胞术检测 PB2 对 OS 细胞系增殖和凋亡的影响。通过 qRT-PCR 和 Western blot 测定靶基因和蛋白表达水平。建立异种移植小鼠模型,评估 PB2 对体内 OS 增殖和凋亡的影响。体外实验结果表明,PB2 抑制 OS 细胞的增殖并诱导其凋亡,同时增加凋亡相关蛋白的表达水平。此外,PB2 通过抑制 PI3K/AKT 信号通路诱导 OS 细胞凋亡。体内实验进一步证实,PB2 能够抑制 OS 肿瘤生长并诱导其凋亡。综上所述,这些结果表明,PB2 通过抑制 PI3K/AKT 信号通路抑制 OS 细胞的增殖并诱导其凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3c2/7579710/91dbf0aff53f/JCMM-24-11960-g001.jpg

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