Mechanism of Action of the Traditional Chinese Medicine Formula Weichang'an in the Treatment of Gastric Cancer Based on TMT Proteomics Analysis

Abstract

Objective The aim of the study was to screen key proteins involved in the treatment of human gastric cancer subcutaneous xenografts in nude mice by the traditional Chinese medicine formula Weichang'an and to explore its mechanism of action in treating gastric cancer.

Methods Sixteen 7- to 8-week-old female BALB/C nude mice were used to establish a human gastric cancer subcutaneous xenograft model by bilateral axillary injection of MKN45 cells. Mice with successfully established tumors were randomly divided into the Weichang'an group and the model group, with eight mice in each group. Mice in the Weichang'an group were orally administered 0.5 mL of Weichang'an decoction, while mice in the model group were given 0.5 mL of normal saline by gavage once a day for 21 consecutive days. On day 28, the animals were sacrificed by cervical dislocation, and tumors were excised to measure tumor weight and assess the tumor suppression rate. Tandem mass tags (TMT) quantitative proteomics was used to analyze the tumor samples, identify differentially expressed proteins, and perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.

Results Compared with the model group, the tumor weight in the Weichang'an group was significantly reduced (p < 0.001), and the tumor suppression rate was 41.40%, indicating that Weichang'an can inhibit the growth of human gastric cancer subcutaneous xenografts in nude mice. TMT quantitative proteomics identified a total of 2,856 proteins, with 13 proteins showing downregulated expression and 25 proteins showing upregulated expression in the Weichang'an group. GO enrichment analysis revealed that differentially expressed proteins were mainly enriched in cellular components such as the cell membrane, extracellular matrix, and envelope, and participated in biological processes like negative regulation of cell adhesion, hematopoiesis, and skeletal system development, with functions in cell adhesion molecule binding and molecular sensor activity. The KEGG pathway enrichment analysis identified the autophagy-lysosome pathway.

Conclusion Weichang'an may exert its therapeutic effect on gastric cancer by regulating the expression of various proteins and modulating the autophagy-lysosome pathway.

Keywords

TMT proteomics - Weichang'an - gastric cancer - differentially expressed protein

CRediT Authorship Contribution Statement

Yaofei Niu contributed to project administration, conceptualization, data curation, formal analysis, and writing the original draft. Weixia Chen and Yajie Ding contributed to funding acquisition, investigation, data curation, formal analysis, validation, and methodology. Yan Xu and Aiguang Zhao contributed to project administration, supervision, and review and editing of the manuscript.

Publikationsverlauf

Eingereicht: 11. August 2024

Angenommen: 22. September 2024

Artikel online veröffentlicht:
30. Dezember 2024

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