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