Effect of Lycium Barbarum Polysaccharide on Ferroptosis and the Nrf2/HO-1 Signaling Pathway in Neuroblastoma Cells
Author：LI Zhanhu1, LI Shuang2
Unit：1.Children's Hospital Affiliated to Xi'an Jiaotong University, Xi'an Shaanxi 710003, China; 2.Xidian Group Hospital, Xi'an Shaanxi 710077, China
Quote：引用：李战虎，李双.枸杞多糖对神经母细胞瘤细胞铁死亡及Nrf2/HO-1信号通路的影响[J].中医药导报,2026, 32(2):19-23.
DOI：10.13862/j.cn43-1446/r.2026.02.004
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Abstract：
Objective: To investigate the effects of
lycium barbarum polysaccharide (LBP) on proliferation, migration, ferroptosis,
and the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1
(HO-1) signaling pathway in neuroblastoma cells. Methods: Cells were treated
with normal saline and 0.5, 1.0, 2.0, 4.0, 8.0, 16.0, 32.0, and 64.0 mg/mL LBP,
respectively. The cell counting kit-8 (CCK-8) assay was used to detect the
viability of SH-SY5Y cells and calculate the half?maximal inhibitory
concentration (IC50). The optimal drug concentrations were screened, and three
concentrations were selected for subsequent experiments. Cell migration was
examined by scratch assay. Western blotting was performed to measure the
protein expression levels of Ki-67, Survivin, matrix metalloproteinase-2
(MMP-2), Vimentin, Fibronectin, cystine/glutamate antiporter (xCT), glutathione
peroxidase 4 (GPX4), divalent metal transporter 1 (DMT1), Nrf2, phosphorylated
Nrf2 (p-Nrf2), and HO-1. Results: Compared with the control group, treatment
with 0.5, 1.0, 2.0, 4.0, 8.0, 16.0, 32.0 and 64.0 mg/mL LBP for 48 h
significantly reduced cell survival. The IC50 of LBP on SH-SY5Y cells was 17.10
μmol/L. Three concentration groups (8, 16, and 32 μmol/L) were chosen for
follow-up experiments. In the 16 μmol/L and 32 μmol/L LBP groups, the
expression levels of Ki-67 and Survivin proteins were significantly decreased;
the scratch healing rate and the expression of MMP-2, Vimentin, and Fibronectin
proteins were significantly reduced; the expression of xCT and GPX4 proteins
was markedly lowered, while DMT1 protein expression was significantly
increased; and the expression levels of p-Nrf2, Nrf2, and HO-1 proteins were
all notably elevated. Conclusion: Lycium barbarum polysaccharide can
significantly inhibit the proliferation, migration, and ferroptosis level of
SH-SY5Y cells, which may be related to the activation of the Nrf2/HO-1
signaling pathway. These findings provide a basis for further exploration of
the pathogenesis of neuroblastoma and the search for new therapeutic
strategies.
Key words：neuroblastoma; lycium barbarum polysaccharide; ferroptosis; Nrf2/HO-1 signaling pathway
摘要：
目的：探究枸杞多糖对神经母细胞瘤细胞增殖、迁移、铁死亡和核转录因子E2相关因子2（Nrf2）/血红素加氧酶-1（HO-1）信号通路的影响。方法：分别用生理盐水以及0.5、1.0、2.0、4.0、8.0、16.0、32.0、64.0 mg/mL枸杞多糖处理细胞，采用细胞活力检测-8（CCK-8）的方法检测枸杞多糖对SH-SY5Y细胞活力的影响并计算半抑制浓度（IC50）值，筛选最佳药物浓度，选取3个浓度进行后续实验。划痕实验检测细胞迁移；蛋白印迹法检测Ki-67、生存素、基质金属蛋白酶-2（MMP2）、波形蛋白、纤连蛋白、胱氨酸／谷氨酸反向转运体（xCT）、谷胱甘肽过氧化物酶4（GPX4）、二价金属离子转运体1（DMT1）、Nrf2、磷酸化核因子E2相关因子2（p-Nrf2）、HO-1的蛋白表达水平。结果：与对照组相比，0.5、1.0、2.0、4.0、8.0、16.0、32.0、64.0 mg/mL枸杞多糖处理48 h细胞存活率明显降低。枸杞多糖对SH-SY5Y细胞的IC50为17.10 μmol/L，选择8、16、32 μmol/L3个浓度组进行后续实验。16 μmol/L和32 μmol/L枸杞多糖组Ki-67蛋白、Survivin蛋白表达水平均显著降低，划痕愈合率和MMP-2、Vimentin蛋白Fibronectin蛋白表达水平均显著降低，xCT、GPX4蛋白表达水平显著降低，而DMT1蛋白表达水平显著升高，p-Nrf2、Nrf2、HO-1蛋白表达水平均显著升高。结论：枸杞多糖可以显著抑制SH-SY5Y细胞增殖、迁移和铁死亡水平，可能与激活Nrf2/HO-1信号通路有关，为进一步探讨神经母细胞瘤的发病机制及寻找新的治疗方案提供依据。
关键词：神经母细胞瘤；枸杞多糖；铁死亡；核转录因子E2相关因子2/血红素加氧酶-1信号通路
Release time：2026-03-05
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