Dataset Information

Modified Gexia-Zhuyu Tang inhibits gastric cancer progression by restoring gut microbiota and regulating pyroptosis.

ABSTRACT:

Background

Gexia-Zhuyu Tang (GZT), a traditional Chinese medicine formula, is used to treat a variety of diseases. However, its roles in gastric cancer (GC) remain unclear.

Objective

The aim of this study was to explore the roles and underlying molecular mechanisms of modified GZT in GC.

Methods

The effects of modified GZT on GC were investigated by constructing mouse xenograft models with MFC cell line. The fecal samples from low-dose, high-dose, and without modified GZT treatment groups were collected for the 16S rRNA gene sequencing and fecal microbiota transplantation (FMT). Histopathological alterations of mice were evaluated using the hematoxylin-eosin (HE). Immunohistochemical (IHC) analysis with Ki67 and GSDMD was performed to measure tissue cell proliferation and pyroptosis, respectively. Proteins associated with pyroptosis, invasion, and metastasis were detected by Western blotting. Enzyme-linked immunosorbent assay (ELISA) was used to assess inflammation-related factors levels.

Results

Modified GZT inhibited GC tumor growth and reduced metastasis and invasion-related proteins expression levels, including CD147, VEGF, and MMP-9. Furthermore, it notably promoted caspase-1-dependent pyroptosis, as evidenced by a dose-dependent increase in TNF-α, IL-1β, IL-18, and LDH levels, along with elevated protein expression of NLRP3, ASC, and caspase-1. Additionally, modified GZT increased species abundance and diversity of the intestinal flora. FMT assay identified that modified GZT inhibited GC tumor progression through regulation of intestinal flora.

Conclusions

Modified GZT treatment may promote pyroptosis by modulating gut microbiota in GC. This study identifies a new potential approach for the GC clinical treatment.

SUBMITTER: Zhao T

PROVIDER: S-EPMC10775600 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Modified Gexia-Zhuyu Tang inhibits gastric cancer progression by restoring gut microbiota and regulating pyroptosis.

Zhao Tingting T Yu Zhijian Z

Cancer cell international 20240109 1

<h4>Background</h4>Gexia-Zhuyu Tang (GZT), a traditional Chinese medicine formula, is used to treat a variety of diseases. However, its roles in gastric cancer (GC) remain unclear.<h4>Objective</h4>The aim of this study was to explore the roles and underlying molecular mechanisms of modified GZT in GC.<h4>Methods</h4>The effects of modified GZT on GC were investigated by constructing mouse xenograft models with MFC cell line. The fecal samples from low-dose, high-dose, and without modified GZT t ...[more]

PMID: 38195483

Similar Datasets

Project description:BackgroundCurcumin has been reported to have activity for prevention and therapy of CRC, yet its underlying mechanisms remain largely unknown. Recently, emerging evidence suggests that the gut microbiota and its metabolites contribute to the causation and progression of Colorectal cancer (CRC). In this study, we aimed to investigate if curcumin affects the tumorigenesis of CRC by modulating gut microbiota and its metabolites.MethodsForty male C57BL/6JGpt mice were randomly divided into four groups: negative control (NC), curcumin control, CRC model, and curcumin treatment (CRC-Cur) groups. CRC mouse model was induced by using azoxymethane (AOM) and dextran sodium sulfate (DSS), and the mice in CRC model and curcumin treatment groups received oral PBS or curcumin (150 mg/kg/day), respectively. Additionally, fecal samples were collected. 16 S rRNA sequencing and Liquid Chromatography Mass Spectrometry (LC-MS)-based untargeted metabolomics were used to observe the changes of intestinal flora and intestinal metabolites.ResultsCurcumin treatment restored colon length and structural morphology, and significantly inhibited tumor formation in AOM/DSS-induced CRC model mice. The 16S rRNA sequencing analysis indicated that the diversity and richness of core and total species of intestinal microflora in the CRC group were significantly lower than those in the NC group, which were substantially restored in the curcumin treatment group. Curcumin reduced harmful bacteria, including Ileibacterium, Monoglobus and Desulfovibrio, which were elevated in CRC model mice. Moreover, curcumin increased the abundance of Clostridia_UCG-014, Bifidobacterium and Lactobacillus, which were decreased in CRC model mice. In addition, 13 different metabolites were identified. Compared to the NC group, ethosuximide, xanthosine, and 17-beta-estradiol 3-sulfate-17-(beta-D-glucuronide) were elevated in the CRC model group, whereas curcumin treatment significantly reduced their levels. Conversely, glutamylleucine, gamma-Glutamylleucine, liquiritin, ubenimex, 5'-deoxy-5'-fluorouridine, 7,8-Dihydropteroic acid, neobyakangelicol, libenzapril, xenognosin A, and 7,4'-dihydroxy-8-methylflavan were decreased in the CRC group but notably upregulated by curcumin. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis revealed enrichment in seven pathways, including folate biosynthesis (P < 0.05).ConclusionsThe gut microecological balance was disrupted in AOM/DSS-induced CRC mice, accompanied by metabolite dysbiosis. Curcumin restored the equilibrium of the microbiota and regulated metabolites, highly indicating that curcumin may alleviate the development of AOM/DSS induced colorectal cancer in mice by regulating intestinal flora homeostasis and intestinal metabolites.

Project description:BackgroundGestational diabetes mellitus (GDM), a severe pregnancy disorder, is a temporary form of diabetes that occurs during gestation. Astragaloside IV (AS IV), a natural and effective composition of Astragalus membranaceus, shows pharmacological effects against diabetes. On the contrary, the effects of AS IV on GDM development are still not clear. This study aims to investigate the role of AS IV in alleviating GDM in rats and determine whether AS IV exerts its anti-GDM properties through the regulation of gut microbiota and metabolite modulation.MethodsThere were six pregnant SD rats in each of the four groups. First, the GDM model was induced by the streptozotocin (STZ, 45 mg/kg) injection on gestational days (GDs) 1-4, and AS IV intervention (10 mg/kg/d) was administered from 6 days before pregnancy until delivery. The measurements of relevant indicators pertaining to GDM symptoms and reproductive outcomes, along with the 16S rRNA sequencing data and LC-MS-based metabolomic profiles, were assessed across all groups.ResultsAfter the 25-day intervention, the GDM model + AS IV group showed significantly decreased fasting blood glucose levels (p = 0.0003), mean insulin levels (p = 0.0001), and insulin resistance index (p = 0.0001). AS IV treatment also decreased the malformation rate (p = 0.0373) and increased the average fetal weight (p = 0.0020) of GDM rats. Compared to the control rats, GDM rats showed a significantly higher abundance of Blautia and Anaerobiospirillum. However, the dramatically elevated abundance of these microorganisms was markedly decreased by AS IV treatment. In contrast, compared to GDM rats without treatment, GDM rats treated with AS IV showed a significantly higher abundance of bacteria (p < 0.05), such as Methanobrevibacter, Dubosiella, and Romboutsia, which are beneficial to the rats. Additionally, we observed dramatically elevated production of metabolites, such as N-acetyl-l-leucine and lithocholic acid, after AS IV treatment through metabolomics analysis (p < 0.05). Furthermore, significant associations between most genera of gut bacteria and the altered levels of the metabolites connected to gut microbiota were also discovered.ConclusionOur study demonstrated that AS IV could be an effective nutritional intervention strategy for targeting gut microbiota and metabolome profiles in GDM and provided experimental evidence supporting the use of AS IV to treat GDM.

Dataset Information

Modified Gexia-Zhuyu Tang inhibits gastric cancer progression by restoring gut microbiota and regulating pyroptosis.

Background

Objective

Methods

Results

Conclusions

Publications

Modified Gexia-Zhuyu Tang inhibits gastric cancer progression by restoring gut microbiota and regulating pyroptosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets