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枸杞糖肽通过下调 SREBP1c 靶向 PER2 抑制胶质母细胞瘤的脂肪生成。

Lycium barbarum glycopeptide targets PER2 to inhibit lipogenesis in glioblastoma by downregulating SREBP1c.

机构信息

Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, 750004, P.R. China.

Department of Neurosurgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, 750004, P.R. China.

出版信息

Cancer Gene Ther. 2023 Aug;30(8):1084-1093. doi: 10.1038/s41417-023-00611-4. Epub 2023 Apr 17.

Abstract

Lycium barbarum polysaccharide (LBP) is a substance with various biological activities extracted from Lycium barbarum. LbGPs are peptidoglycans with a short peptide backbone and a complex, branched glycan moiety, which is further extracted and isolated from LBPs. Previous studies have shown that LbGP can inhibit cancer cell growth, but its specific mechanism is not completely clear. In this study, we found that LbGP could inhibit the proliferation of glioma cells and promote the expression of period 2 (PER2) through the PKA-CREB pathway. In addition, LbGP could inhibit the de novo synthesis of lipids by downregulating SREBP1c and its target genes, which depended on the expression of PER2. Moreover, PER2 negatively regulated the expression of SREBP1c via suppressing PI3K/AKT/mTOR pathway. In summary, LbGP may upregulate the expression of PER2 to reduce the expression of SREBP1c, inhibit lipid synthesis in glioblastoma, and inhibit glioblastoma cell proliferation. This study provides an alternative drug for the treatment of glioma and elucidates its potential mechanism.

摘要

枸杞多糖(LBP)是从枸杞中提取的具有多种生物活性的物质。LbGPs 是具有短肽主链和复杂分支聚糖部分的肽聚糖,它是从 LBPs 中进一步提取和分离得到的。先前的研究表明,LbGP 可以抑制癌细胞生长,但具体机制尚不完全清楚。在这项研究中,我们发现 LbGP 可以通过 PKA-CREB 途径抑制神经胶质瘤细胞的增殖并促进周期蛋白 2(PER2)的表达。此外,LbGP 通过下调 SREBP1c 及其靶基因来抑制脂质的从头合成,这依赖于 PER2 的表达。此外,PER2 通过抑制 PI3K/AKT/mTOR 通路负调控 SREBP1c 的表达。总之,LbGP 可能通过上调 PER2 的表达来降低 SREBP1c 的表达,抑制神经胶质瘤中的脂质合成,从而抑制神经胶质瘤细胞的增殖。本研究为治疗神经胶质瘤提供了一种替代药物,并阐明了其潜在的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0e9/10425286/aa0ead41d433/41417_2023_611_Fig1_HTML.jpg

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