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糙皮侧耳子实体多糖通过调控 ARHI 抑制 PI3K/AKT 信号通路抑制神经胶质瘤。

Schizophyllum commune fruiting body polysaccharides inhibit glioma by mediating ARHI regulation of PI3K/AKT signalling pathway.

机构信息

Department of Neurosurgery, Fujian Medical University Union Hospital, 29# Xinquan Road, Fuzhou 350001, Fujian, China.

Fujian Institute of Neurosurgery, 29# Xinquan Road, Fuzhou 350001, Fujian, China.

出版信息

Int J Biol Macromol. 2024 Nov;279(Pt 3):135326. doi: 10.1016/j.ijbiomac.2024.135326. Epub 2024 Sep 3.

DOI:10.1016/j.ijbiomac.2024.135326
PMID:39236963
Abstract

Glioma poses a serious threat to human health and has a high mortality rate. Therefore, developing natural anti-tumour drugs for cancer treatment is an urgent priority. Schizophyllum commune is an edible and medicinal fungus, with polysaccharides as its main active components, which may have anti-tumour properties. Herein, we characterised S. commune fruiting body polysaccharides (SCFP) structure and evaluated its anti-glioma activity in vitro and in vivo. UV and FTIR spectra, high-performance gel chromatography, and monosaccharide composition analyses demonstrated that SCFP was a heteropolysaccharide with a molecular weight of 290.92 kDa. Among the monosaccharide compositions, mannose, galactose, and glucose were the most abundant. SCFP significantly inhibited the survival of the glioma cell lines U251 and U-87MG. U251 xenograft tumours treated with SCFP via gavage showed a 47.39 % inhibition, with no significant toxic side effects observed. SCFP upregulated aplasia Ras homologue member I (ARHI) expression, thereby regulating PI3K/AKT signalling, inhibiting tumour migration, and inducing apoptosis, to inhibit tumour growth. Furthermore, SCFP treatment increased the relative abundance of beneficial bacteria, including Akkermansia muciniphila, Ligilactobacillus murinus, and Parabacteroides goldsteinii, in tumour-bearing mice and restored the gut microbiota structure to that of the normal group (NG group) mice without tumours. Thus, SCFP has the potential for application as a natural anticancer drug.

摘要

神经胶质瘤严重威胁人类健康,致死率高。因此,开发用于癌症治疗的天然抗肿瘤药物是当务之急。裂褶菌是一种药食两用真菌,其主要活性成分为多糖,可能具有抗肿瘤特性。本研究对裂褶菌子实体多糖(SCFP)的结构进行了表征,并在体外和体内评估了其抗神经胶质瘤活性。紫外和傅里叶变换红外光谱、高效凝胶色谱和单糖组成分析表明,SCFP 是一种杂多糖,分子量为 290.92 kDa。在单糖组成中,甘露糖、半乳糖和葡萄糖含量最丰富。SCFP 显著抑制神经胶质瘤细胞系 U251 和 U-87MG 的存活。通过灌胃给予 SCFP 治疗 U251 异种移植瘤,抑制率为 47.39%,未见明显毒副作用。SCFP 上调抑癌基因 Ras 相关结构域家族成员 I(ARHI)的表达,从而调节 PI3K/AKT 信号通路,抑制肿瘤迁移,诱导细胞凋亡,抑制肿瘤生长。此外,SCFP 处理增加了荷瘤小鼠中有益菌的相对丰度,包括黏蛋白阿克曼菌、鼠李糖乳杆菌和黄金色拟杆菌,恢复了肠道微生物群落结构至无肿瘤的正常组(NG 组)小鼠水平。因此,SCFP 具有作为天然抗癌药物的应用潜力。

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