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阴沟肠杆菌多糖通过激活 p53 和线粒体内在途径诱导人骨肉瘤细胞凋亡。

A polysaccharide from Enterobacter cloacae induces apoptosis of human osteosarcoma cells through the activation of p53 and mitochondrial intrinsic pathway.

机构信息

Department of Orthopedics Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, Guangdong, China.

Laboratory of Pathogenic Biology, Guangdong Medical University, Zhanjiang 524023, Guangdong, China.

出版信息

Int J Biol Macromol. 2019 Feb 1;122:58-63. doi: 10.1016/j.ijbiomac.2018.10.111. Epub 2018 Oct 16.

Abstract

In the present study, a polysaccharide (ECP) from Enterobacter cloacae dose and time-dependently inhibited cell growth of human osteosarcoma U-2 OS cells via induction of apoptosis. ECP treatment was selectively toxic to U-2 OS cells whereas had no cytotoxic effect on normal human osteoblast cell line NHOst. ECP-induced apoptotic cell death was associated with collapse of mitochondrial membrane, cytochrome c release into the cytosol, activation of caspase-9 and-3, degradation of poly (ADP-ribose) polymerase (PARP), elevated the ratio of Bax/Bcl-2 protein and overexpression of p53, suggesting the involvement of the activation of p53 and mitochondrial intrinsic pathway in ECP-induced apoptosis. Likewise, ECP oral administration significantly inhibited the U-2 OS cancer growth in xenograft tumor model. All these first evidence indicated that ECP was a potential antitumor supplement for the treatment of human osteosarcoma.

摘要

在本研究中,阴沟肠杆菌来源的多糖(ECP)通过诱导细胞凋亡,呈剂量和时间依赖性地抑制人骨肉瘤 U-2 OS 细胞的生长。ECP 处理对 U-2 OS 细胞具有选择性毒性,而对正常的人成骨细胞系 NHOst 没有细胞毒性作用。ECP 诱导的细胞凋亡死亡与线粒体膜崩溃、细胞色素 c 释放到细胞质、半胱天冬酶-9 和 -3 的激活、多聚(ADP-核糖)聚合酶(PARP)的降解、Bax/Bcl-2 蛋白比率升高以及 p53 的过表达有关,提示 p53 和线粒体内在途径的激活参与了 ECP 诱导的细胞凋亡。同样,ECP 口服给药显著抑制了异种移植肿瘤模型中的 U-2 OS 肿瘤生长。所有这些初步证据表明,ECP 是治疗人类骨肉瘤的一种有潜力的抗肿瘤补充剂。

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