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羟基磷灰石纳米颗粒通过下调FAK/PI3K/Akt信号通路在体外和体内的抗骨肉瘤作用

Anti-osteosarcoma effect of hydroxyapatite nanoparticles both in vitro and in vivo by downregulating the FAK/PI3K/Akt signaling pathway.

作者信息

Wang Renxian, Liu WeiFeng, Wang Qian, Li Guangping, Wan Ben, Sun Yuyang, Niu Xiaohui, Chen Dafu, Tian Wei

机构信息

Laboratory of Bone Tissue Engineering, Beijing Laboratory of Biomedical Materials, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Beijing 100035, China.

出版信息

Biomater Sci. 2020 Aug 21;8(16):4426-4437. doi: 10.1039/d0bm00898b. Epub 2020 Jul 3.

Abstract

Numerous studies have reported that hydroxyapatite nanoparticles (nano-HAPs) can inhibit the proliferation of a variety of tumor cells and this effect is different in different carcinoma cells. However, the effect of nano-HAPs on osteosarcoma cell proliferation has not been well understood thus far. In this study, we first showed that our synthesized nano-HAPs reduced cell viability and inhibited migration and invasion of OS-732 cells in a concentration-dependent manner. Using a BALB/c nude mouse tumor model, we demonstrated that nano-HAPs could effectively suppress tumor growth in vivo. We also performed RNA-seq analysis to investigate the underlying mechanism of these effects and discovered that treatment of OS-732 cells with nano-HAPs significantly downregulated the FAK/PI3K/Akt signaling pathway. Collectively, our study suggests that treatment with nano-HAPs can inhibit osteosarcoma cell growth, migration and invasion in vitro and suppress osteosarcoma in vivo.

摘要

大量研究报道,羟基磷灰石纳米颗粒(纳米HAPs)可抑制多种肿瘤细胞的增殖,且这种作用在不同癌细胞中有所不同。然而,迄今为止,纳米HAPs对骨肉瘤细胞增殖的影响尚未完全明确。在本研究中,我们首先表明,我们合成的纳米HAPs以浓度依赖的方式降低了细胞活力,并抑制了OS-732细胞的迁移和侵袭。使用BALB/c裸鼠肿瘤模型,我们证明纳米HAPs可有效抑制体内肿瘤生长。我们还进行了RNA测序分析以研究这些作用的潜在机制,发现用纳米HAPs处理OS-732细胞可显著下调FAK/PI3K/Akt信号通路。总体而言,我们的研究表明,纳米HAPs处理可在体外抑制骨肉瘤细胞的生长、迁移和侵袭,并在体内抑制骨肉瘤。

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