研究动态
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通过特定的三螺旋β-葡聚糖诱导的p53依赖性通路,抑制人类宫颈癌发展。

Inhibition of human cervical cancer development through p53-dependent pathways induced by the specified triple helical β-glucan.

发表日期:2023 Aug 14
作者: Shuqian Hu, Hui Xu, Conghua Xie, Yan Meng, Xiaojuan Xu
来源: Int J Biol Macromol

摘要:

本研究表明,从人工培养的香菇中提取和纯化的具有三级螺旋结构和相对较窄分子量分布的β-葡聚糖(LNT),在体外和体内显示出对宫颈癌的显著抑制作用,对正常细胞的细胞毒性较小。从体外数据中,初步揭示了抗宫颈癌的潜在机制如下:LNT首先被人类宫颈癌细胞系Hela识别,并通过p21诱导细胞增殖抑制,通过针对肿瘤抑制因子p53通过线粒体依赖途径诱导细胞凋亡,由增加活性氧(ROS)产生和线粒体膜电位(Δψm)丧失在显著剂量依赖性的方式下指示;同时,LNT通过上调p53,Bax,细胞周期蛋白c,caspase 9 和caspase 3的表达,以及下调Bcl-2,MDM2和PARP1水平,通过内源性MDM2/p53/Bax/线粒体信号通路,抑制BALB/c裸小鼠移植了Hela细胞的肿瘤生长,抑制率为61.2 % ,并诱导肿瘤细胞凋亡。本研究为LNT作为潜在药物候选提供了科学依据,其具有三级螺旋结构、指定的分子量和相对较窄的分布,可用于宫颈癌的临床治疗。版权所有© 2023 Elsevier B.V.。
This study demonstrates that the purified β-glucan (LNT) with a triple helix and relatively narrow molecular weight distribution, extracted and purified from artificially cultured Lentinus edodes, showed a significant cervical cancer inhibition with little cytotoxicity against normal cells in vitro and in vivo. From the in vitro data, the potential mechanism of anti-cervical cancer was preliminarily revealed as follows: LNT was firstly recognized by the human cervical cancer cell line of Hela and induced cell proliferation inhibition through p21 and apoptosis via a mitochondrion-dependent pathway by targeting the tumor suppressor of p53, indicated by an increase in reactive oxygen species (ROS) generation and a loss of mitochondrial membrane potential (Δψm), in a significant dosage dependent manner; Meanwhile, LNT repressed tumor growth with an inhibition ratio of 61.2 % and induced tumor cell apoptosis through endogenous MDM2/p53/Bax/mitochondrion signal pathway by up-regulating the expression of p53, Bax, Cyt. c, caspase 9, and caspase 3, as well as down-regulating Bcl-2, MDM2, and PARP1 levels in Hela cells-transplanted BALB/c nude mice. This study provides a scientific basis LNT as a potential drug candidate characterized by the triple helix and specified molecular weight with a relatively narrow distribution in clinical treatment of cervical cancer.Copyright © 2023. Published by Elsevier B.V.