World journal of gastroenterology · 2026
Pristimerin ameliorates spasmolytic polypeptide-expressing metaplasia by modulating Cdkn1c (p57)-mediated glycolytic reprogramming.
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Wen Jun-Song, Pan Zi-Wei, Yao Xue-Dan, Liu Yan-Qing, Zhu Yao-Dong
Аннотация
BACKGROUND: Spasmolytic polypeptide-expressing metaplasia (SPEM) is a gastric precancerous lesion (GPL) with high malignant potential. The ethyl acetate extract of Celastrus orbiculatus Thunb. effectively ameliorates GPL and gastric cancer progression. Meanwhile, the primary active constituent of this plant, pristimerin, also demonstrates notable antitumor activity.
AIM: To investigate the therapeutic effects of pristimerin on SPEM and its underlying mechanisms.
METHODS: Pristimerin was administered to high-dose tamoxifen-induced SPEM mice to assess its effects on pathological progression, glycolytic reprogramming, and Cdkn1c (p57) expression. Human gastric epithelial (GES-1) cells were treated with tamoxifen and then with pristimerin or 2-deoxy-D-glucose to demonstrate that pristimerin ameliorates SPEM by regulating glycolytic reprogramming. Furthermore, gastric organoids were treated with N-methyl-N'-nitro-N-nitrosoguanidine/Helicobacter pylori, followed by Cdkn1c overexpression or knockdown and then pristimerin, to confirm p57 as the key target through which pristimerin regulates glycolytic reprogramming and reverses SPEM.
RESULTS: Pristimerin effectively ameliorated gastric mucosal damage and oxyntic atrophy induced by high-dose tamoxifen, suppressed the aberrant upregulation of key glycolytic regulators, SPEM-specific markers, and stem cell markers, and upregulated p57 expression. In tamoxifen-induced GES-1 cells, pristimerin exhibited comparable therapeutic effects. Crucially, glycolysis inhibition in GES-1 cells effectively ameliorated tamoxifen-induced SPEM-associated phenotypes. In gastric organoids, Cdkn1c overexpression suppressed glycolytic reprogramming and SPEM phenotype activation, whereas Cdkn1c knockdown attenuated pristimerin-mediated inhibition of glycolysis and amelioration of SPEM.
CONCLUSION: Pristimerin effectively ameliorates gastric mucosal pathological damage and oxyntic atrophy in high-dose tamoxifen-induced SPEM mice, and improves SPEM progression by modulating Cdkn1c (p57)-mediated glycolytic reprogramming.
AIM: To investigate the therapeutic effects of pristimerin on SPEM and its underlying mechanisms.
METHODS: Pristimerin was administered to high-dose tamoxifen-induced SPEM mice to assess its effects on pathological progression, glycolytic reprogramming, and Cdkn1c (p57) expression. Human gastric epithelial (GES-1) cells were treated with tamoxifen and then with pristimerin or 2-deoxy-D-glucose to demonstrate that pristimerin ameliorates SPEM by regulating glycolytic reprogramming. Furthermore, gastric organoids were treated with N-methyl-N'-nitro-N-nitrosoguanidine/Helicobacter pylori, followed by Cdkn1c overexpression or knockdown and then pristimerin, to confirm p57 as the key target through which pristimerin regulates glycolytic reprogramming and reverses SPEM.
RESULTS: Pristimerin effectively ameliorated gastric mucosal damage and oxyntic atrophy induced by high-dose tamoxifen, suppressed the aberrant upregulation of key glycolytic regulators, SPEM-specific markers, and stem cell markers, and upregulated p57 expression. In tamoxifen-induced GES-1 cells, pristimerin exhibited comparable therapeutic effects. Crucially, glycolysis inhibition in GES-1 cells effectively ameliorated tamoxifen-induced SPEM-associated phenotypes. In gastric organoids, Cdkn1c overexpression suppressed glycolytic reprogramming and SPEM phenotype activation, whereas Cdkn1c knockdown attenuated pristimerin-mediated inhibition of glycolysis and amelioration of SPEM.
CONCLUSION: Pristimerin effectively ameliorates gastric mucosal pathological damage and oxyntic atrophy in high-dose tamoxifen-induced SPEM mice, and improves SPEM progression by modulating Cdkn1c (p57)-mediated glycolytic reprogramming.