Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Oct 24, 2024; 15(10): 1293-1308
Published online Oct 24, 2024. doi: 10.5306/wjco.v15.i10.1293
Banxia xiexin decoction prevents the development of gastric cancer
Guo-Xiu Zu, Ke-Yun Sun, Xi-Jian Liu, Ji-Qin Tang, Hai-Liang Huang, Tao Han
Guo-Xiu Zu, Ke-Yun Sun, Xi-Jian Liu, Tao Han, College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
Ji-Qin Tang, Hai-Liang Huang, School of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong Province, China
Co-corresponding authors: Hai-Liang Huang and Tao Han.
Author contributions: Zu GX and Sun KY contributed to methodology, investigation, writing, review and editing; Liu XJ contributed to visualization, validation, writing, review and editing; Zu GX writing the original draft, data curation; Sun KY contributed to software, and formal analysis; Tang JQ contributed to resources and writing, review editing; Huang HL contributed to supervision, funding acquisition, writing, review and editing; Han T contributed to funding acquisition, conceptualization, writing review, and editing; Huang HL and Han T contributed equally to the study as co-corresponding authors; All authors have reviewed and approved the final version of the manuscript.
Supported by the Key Program of Shandong Province, China, No. 2016CYJS08A01-6.
Institutional review board statement: This study was exempted by the Ethics Committee of Shandong University of Traditional Chinese Medicine due to its not involving human subject research.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Center of Experiment, Shandong University of Traditional Chinese Medicine, IACUC protocol: No. SDUTCM20230828016.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: The original RNA-seq data used in this paper has been uploaded to NCBI database (https://www.ncbi.nlm.nih.gov/).
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hai-Liang Huang, Doctor, MD, PhD, Dean, School of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, No. 4655 Daxue Road, Jinan 250355, Shandong Province, China. 1615080865@qq.com
Received: June 13, 2024
Revised: August 9, 2024
Accepted: August 23, 2024
Published online: October 24, 2024
Processing time: 107 Days and 21.5 Hours
Abstract
BACKGROUND

In China banxia xiexin decoction (BXD) has been used in treating gastric cancer (GC) for thousands of years and BXD has a good role in reversing GC histopathology, but its chemical composition and action mechanism are still unknown.

AIM

To investigate the mechanism of action of BXD against GC based on transcriptomics, network pharmacology, in vivo and in vitro experiments.

METHODS

The transplanted tumor model was prepared, and the nude mouse were pathologically examined after administration, and hematoxylin-eosin staining was performed. The active ingredients of BXD were quality controlled and identified using ultra-performance liquid chromatography tandem quadrupole electrostatic field orbitrap mass spectrometry (UPLC-Q-Orbitrap MS/MS), and traditional Chinese medicines systems pharmacology platform, drug bank and the Swiss target prediction platform to predict the relevant targets, the differentially expressed genes (DEGs) of GC were screened by RNA-seq sequencing, and the overlapping targets were analyzed to obtain the key targets and pathways. Cell Counting Kit-8, apoptosis assay, cell migration and Realtime fluorescence quantitative polymerase chain reaction were used for in vitro experiments.

RESULTS

All dosing groups inhibited the growth of transplanted tumors in laboratory-bred strain nude, with the capecitabine group and the BXD medium-dose group being the best. A total of 29 compounds and 859 potential targets in BXD were identified by UPLC-Q-Orbitrap MS/MS and network pharmacology, RNA-seq sequencing found 4767 GC DEGs, which were combined with network pharmacology and analyzed 246 potential therapeutic targets were obtained and pathway results showed that BXD may against GC through the Phosphoinositide 3-kinase (PI3K)/protein kinase B (AKt) signaling pathway. In vitro cellular experiments confirmed that BXD-containing serum and LY294002 could inhibit the proliferation of GC cells, promote apoptosis, and inhibit the migration of GC cells by decreasing the expression of EGFR, PIK3CA, IL6, BCL2 and AKT1 in the PI3K-Akt pathway in MGC-803 expression.

CONCLUSION

BXD has the effect of inhibiting tumor growth rate and delaying the development of GC. Its mechanism of action may be related to the regulation of PI3K-Akt signaling pathway.

Keywords: Banxia xiexin decoction; Gastric cancer; Ultra-performance liquid chromatography tandem quadrupole electrostatic field orbitrap mass spectrometry; Network pharmacology; Whole transcriptomic sequencing; Phosphoinositide 3-kinase/protein kinase B signaling pathway

Core Tip: Based on the clinical efficacy of traditional Chinese medicine banxia xiexin decoction (BXD) in the prevention and treatment of gastric cancer, this paper explored the drug composition and drug authenticity of BXD based on Ultra-performance liquid chromatography tandem quadrupole electrostatic field orbitrap mass spectrometry technology, predicted the molecular mechanism of BXD in the treatment of gastric cancer based on network pharmacology and transcriptomics sequencing, and verified its molecular mechanism by combining in vivo and in vitro experiments.