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黄连与干姜的组合通过干扰 LDHA 和 SLC2A1 葡萄糖代谢来抑制胃肿瘤生长。

Coptis chinensis and dried ginger herb combination inhibits gastric tumor growth by interfering with glucose metabolism via LDHA and SLC2A1.

机构信息

Hubei Engineering Technology Research Center of Chinese Materia Medica Processing, College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China.

Hubei Engineering Technology Research Center of Chinese Materia Medica Processing, College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China.

出版信息

J Ethnopharmacol. 2022 Feb 10;284:114771. doi: 10.1016/j.jep.2021.114771. Epub 2021 Nov 2.

DOI:10.1016/j.jep.2021.114771
PMID:34737010
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Coptis chinensis Franch (CC) and Zingiber officinale Roscoe (dried ginger; DG) are traditional Chinese medicines. CC can dry dampness, relieve fire and detoxify, and is used to treat gastritis, gastric ulcer, colitis. DG can warm spleen and stomach for dispelling cold, used for the treatment of spleen and stomach deficiency. Both CC and DG are widely used to treat gastrointestinal diseases. CC-DG herb medicine combination originates from Huanglian decoction and Pinellia xiexin decoction in "Shanghan Lun" to comfort the stomach and intestines. CC and DG are used for the treatment of nausea and choking diaphragm which highly associated with gastric cancer clinically in ancient time.

AIM OF THE STUDY

This study aimed to investigate the effects and underlying molecular mechanisms of CC-DG combination on gastric cancer.

MATERIALS AND METHODS

The CC-DG extract was subjected to HPLC analysis. Viability (MTT) and cytotoxicity (CCK8) assays were performed using the SGC7901 and MFC cells. Cell cycle and apoptosis were measured by flow cytometry. The mRNA expression levels were measured by RT-PCR. In vivo anti-tumor activity of CC-DG was assessed in a tumor xenograft model.

RESULTS

Twelve different proportions of CC-DG were tested for inhibitory effects on gastric cancer cells; CC-DG ratio 1:1 was found most effective. CC-DG administration significantly reduced the cell proliferation, migration, and colony formation, while increased cell apoptosis compared with the control group. CC-DG regulated differentially expressed genes in SGC7901 cells were subjected to pathway enrichment analysis. CC-DG significantly inhibited the cell glucose metabolism, downregulated the expression of LDHA and SLC2A1 genes, and changed the expression of other related genes including ME2, LDHD, LDHB, HIF1A, PKM, Pcx, and Got1. In addition, CC-DG suppressed tumorigenesis and inhibited MKI67 expression in the tumor xenograft model.

CONCLUSIONS

CC-DG inhibited the proliferation, migration, invasion of SGC7901/MFC gastric cells, and in turn, suppressed tumorigenesis by regulating glucose metabolism through regulation of LDHA and SLC2A1 genes.

摘要

药用植物学相关性

黄连(Coptis chinensis Franch)和干姜(Zingiber officinale Roscoe,干生姜)是两种传统的中国草药。黄连可以燥湿、泻火解毒,用于治疗胃炎、胃溃疡、结肠炎。干姜可以温中散寒,用于治疗脾胃虚寒。黄连和干姜广泛用于治疗胃肠道疾病。黄连-干姜药对源自《伤寒论》中的黄连汤和半夏泻心汤,可起到和胃止呕的作用。黄连和干姜在古代临床上常用于治疗与胃癌高度相关的恶心、噎膈。

研究目的

本研究旨在探讨黄连-干姜药对治疗胃癌的作用及潜在的分子机制。

材料和方法

采用高效液相色谱法对黄连-干姜提取物进行分析。采用 MTT 和 CCK8 法检测 SGC7901 和 MFC 细胞活力和细胞毒性。通过流式细胞术检测细胞周期和凋亡。采用 RT-PCR 检测 mRNA 表达水平。在肿瘤异种移植模型中评估黄连-干姜的体内抗肿瘤活性。

结果

测试了 12 种不同比例的黄连-干姜对胃癌细胞的抑制作用,发现黄连-干姜比例为 1:1 时效果最佳。与对照组相比,黄连-干姜给药组显著降低了细胞增殖、迁移和集落形成能力,同时增加了细胞凋亡。对 SGC7901 细胞中差异表达基因进行通路富集分析。黄连-干姜显著抑制细胞葡萄糖代谢,下调 LDHA 和 SLC2A1 基因表达,并改变 ME2、LDHD、LDHB、HIF1A、PKM、Pcx 和 Got1 等其他相关基因的表达。此外,黄连-干姜在肿瘤异种移植模型中抑制肿瘤发生,抑制 MKI67 表达。

结论

黄连-干姜通过调节 LDHA 和 SLC2A1 基因抑制 SGC7901/MFC 胃细胞的增殖、迁移和侵袭,从而抑制肿瘤发生。

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