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从星虫中提取的新型多糖通过增强免疫功能和诱导肿瘤细胞凋亡来抑制体内 HepG2 肿瘤的生长。

Novel polysaccharide extracted from Sipunculus nudus inhibits HepG2 tumour growth in vivo by enhancing immune function and inducing tumour cell apoptosis.

机构信息

Key Laboratory of Cultivation and High-value Utilization of Marine Organisms in Fujian Province, Fisheries Research Institute of Fujian, Xiamen, China.

Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Zhuhai Key Laboratory of Marine Bioresources and Environment, School of Marine Sciences, Sun Yat-Sen University, Guangzhou, China.

出版信息

J Cell Mol Med. 2021 Sep;25(17):8338-8351. doi: 10.1111/jcmm.16793. Epub 2021 Jul 24.

Abstract

A novel polysaccharide was extracted from Sipunculus nudus (SNP). The molecular weight (MW) of SNP was determined to be 9223 Da by high-performance gel permeation chromatography analyses, and the structure of the SNP repeat units was determined to be →3,4-β-D-GlcpNAC (1→ and →4) -α-D-Glcp (1→ in the ratio of 15:1; →2) -α -D-Galp - (1→ as a side chain; and β-D-Galp-(1→ and α- D-Glcp - (1→ as end groups by GC-MS analysis and NMR assays. The effect of SNP on hepatoma HepG2-bearing mice was analysed to verify its potential in the clinical treatment of liver cancer. A total of 90 male athymic nu/nu mice were divided into therapeutic and preventive groups and fed with different amounts of SNP. The antitumour effect of SNP on HepG2-bearing mice and mechanism of such were studied by analysing the tumour size, spleen index, thymus index, immune factors in the blood, tumour apoptosis factors, etc. The results suggest that SNP not only increased the index of immune organs in the body, but also enhanced the secretion of immune factors, including interleukin-2, interferon gamma and tumour necrosis factor-alpha in the serum. SNP induced the apoptosis of tumour cells via the mitochondrial apoptosis pathway, which upregulated caspase-3, caspase-8, caspase-9 and BCL2-associated X, but downregulated B-cell lymphoma-2 and vascular endothelial growth factor protein expression. In conclusion, SNP inhibited tumour growth by enhancing immune function and inducing tumour cell apoptosis in HepG2-bearing mice. Therefore, SNP may be further investigated as a promising candidate for future antitumour drugs.

摘要

从星虫(Sipunculus nudus)中提取出一种新型多糖。通过高效凝胶渗透色谱分析,确定 SNP 的分子量(MW)为 9223 Da,并且 SNP 重复单元的结构被确定为→3,4-β-D-GlcpNAC(1→和→4)-α-D-Glcp(1→的比例为 15:1;→2)-α-D-Galp-(1→作为侧链;β-D-Galp-(1→和α-D-Glcp-(1→作为末端基团通过 GC-MS 分析和 NMR 分析。分析 SNP 对肝癌 HepG2 荷瘤小鼠的作用,验证其在肝癌临床治疗中的潜力。将 90 只雄性无胸腺 nu/nu 小鼠分为治疗组和预防组,并给予不同剂量的 SNP。通过分析肿瘤大小、脾指数、胸腺指数、血液中的免疫因子、肿瘤凋亡因子等,研究 SNP 对 HepG2 荷瘤小鼠的抗肿瘤作用及其机制。结果表明,SNP 不仅增加了体内免疫器官的指数,而且增强了免疫因子的分泌,包括血清中的白细胞介素-2、干扰素γ和肿瘤坏死因子-α。SNP 通过线粒体凋亡途径诱导肿瘤细胞凋亡,上调半胱氨酸天冬氨酸蛋白酶-3、半胱氨酸天冬氨酸蛋白酶-8、半胱氨酸天冬氨酸蛋白酶-9 和 B 细胞淋巴瘤-2 相关 X,但下调 B 细胞淋巴瘤-2 和血管内皮生长因子蛋白的表达。总之,SNP 通过增强免疫功能和诱导 HepG2 荷瘤小鼠肿瘤细胞凋亡来抑制肿瘤生长。因此,SNP 可能作为一种有前途的抗肿瘤药物候选物进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de95/8419178/77ee085c5bb6/JCMM-25-8338-g008.jpg

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