Validation and analysis of key factors of Banxia Xiexin decoction against gastric cancer

半夏泻心汤抗胃癌关键因素的验证与分析

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作者:Guo-Xiu Zu ,Ji-Qin Tang ,Hai-Liang Huang ,Tao Han

Abstract

Background: In China Banxia Xiexin decoction (BXD) has been used in treating gastric cancer (GC) for thousands of years. BXD has been shown to reverse GC histopathology, but its chemical composition and action mechanism are still unknown. Aim: To investigate the mechanism of BXD against GC based on utilizing transcriptomics and proteomics techniques experiments. Methods: Using the AGS cell line as the model group, the Cell Counting Kit-8 method and Annexin V-AbFluor™ were employed 488/propidium iodide double staining method was used to detect the levels of cell proliferation and apoptosis. Differential expression genes and differentially expressed proteins before and after BXD intervention were detected using RNA-seq and Pro DIA techniques. Key transcription factors were identified by enrichment and analysis using Metascape, and the key pathways were validated by western blot and reverse transcription PCR in vitro and in vivo experiments. Results: BXD significantly inhibited the proliferation rate and migration rate of GC cells and promoted cell apoptosis. The comprehensive analysis of transcriptomics and proteomics showed that five transcription factors, namely phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, phosphoinositide-3-kinase regulatory subunit 1, AKT serine/threonine kinase 1, heat shock protein 90 alpha family class A member 1, and tumor protein p53, were key factors in BXD-mediated anti-cancer therapy and participated in the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. In vitro experiments were conducted using LY294002, an inhibitor of the PI3K/AKT signaling pathway, to validate the expression of five transcription factors at the protein and mRNA levels. In vivo experiments have shown that BXD inhibits tumor growth and suppresses the expression of the PI3K/AKT signaling pathway. Conclusion: Transcriptomic and proteomic analysis showed that BXD inhibited tumor growth and slowed cancer progression by suppressing five factors in the PI3K/AKT signaling pathway, including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, phosphoinositide-3-kinase regulatory subunit 1, and AKT serine/threonine kinase 1. Keywords: Banxia Xiexin decoction; Gastric cancer; Inflammatory factors; Proteomics; Transcriptomics.

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