Ethnopharmacological relevance: The incidence of gastric carcinoma (GC) is increasing rapidly. Traditional Chinese Medicine (TCM) plays a unique role in the treatment of GC. At present, Gancao Xiexin Decoction (GCXXD) has been proved to have a good therapeutic effect on diseases of the spleen and stomach system, but relevant molecular mechanisms remain incompletely explained.
Aim of study: The mechanism of GCXXD for GC was investigated by network pharmacology and verified by cell experiments.
Materials and methods: Firstly, the public database was used to identify the core targets and key pathways of GCXXD in treating GC, followed by molecular docking and survival analysis. Subsequently, the effects of GCXXD on human gastric cancer AGS and HGC-27 cells were confirmed by a series of experiments, such as CCK-8, colony formation, apoptosis, cell cycle, wound scratch assay, transwell chamber assay, qRT-PCR and Western blot.
Results: This study identified quercetin, wogonin, kaempferol, baicalein, sitosterol and beta-sitosterol as key ingredients, along with AKT1, TP53, JUN, STAT3, TNF, MAPK3, HSP90AA1 and EGFR as co targets, and the JAK/STAT signalling pathway as the key pathway. The experimental results showed that GCXXD inhibited the growth of GC cells, increased the apoptosis rate and the ratio of G0/G1 phase cells, and weakened the clone formation rate and inhibited cell migration and invasion. It also reduces the expression of core target genes and downregulates the expression of JAK2, p-JAK2, STAT3, and p-STAT3 proteins.
Conclusion: GCXXD inhibits GC cell growth, reduces clonogenic capacity, induces apoptosis, blocks the cell cycle, and decreases cell migration and invasion rates by inhibiting the JAK2/STAT3 signalling pathway.
Keywords: Gancao Xiexin Decoction; Gastric carcinoma; JAK2/STAT3; Molecular docking; Network pharmacology.
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