Metabolomic Study on Nude Mice Models of Gastric Cancer Treated with Modified Si Jun Zi Tang via HILIC UHPLC-Q-TOF/MS Analysis

Abstract

Recently, metabolomic methods have been used to explore the complex pathogenesis of cancer and the mechanism of action of traditional Chinese medicine (TCM) formulae. In this study, first, modified Si Jun Zi Tang (MSJZT) was prepared with strict quality control using the instrument method of ultra performance liquid chromatography and photodiode array detector (UPLC-PDA). Subsequently, in vivo experiments with tumour-bearing nude mice demonstrated that MSJZT exerted good antitumour effects. MSJZT not only significantly increased mouse body weight but also shrank the tumour volume. Then, the HILIC UHPLC-Q-TOF/MS-based metabolomics approach was used for exploring the pathogenesis of gastric cancer and the molecular mechanism of MSJZT. A total of 59 potential biomarkers in plasma were identified, and 6 pathways were found to be disturbed in gastric cancer. In contrast, after 3 weeks of MSJZT intervention, 32 potential biomarkers were identified, and 4 altered pathways were detected. The changes in glycolytic, amino acid, and lipid metabolisms could be partially regulated by MSJZT through decreasing the content of lactic dehydrogenase (LDH), glutamine synthetase (GS), phosphocholine cytidylyltransferase (PCYT2) mRNA, and protein level. In conclusion, we established a HILIC UHPLC-Q-TOF/MS metabolomic analysis method to demonstrate a complex metabolic profile of gastric cancer. The disordered metabolism could be partially regulated by MSJZT. These findings not only establish a solid foundation for TCM to treat gastric cancer but also provide a basis for further exploration of the precise mechanism of MSJZT activity.

OMICS Applications for Medicinal Plants in Gastrointestinal Cancers: Current Advancements and Future Perspectives

“…HILIC and UHPLC-Q-TOF/MS-based metabolomics approaches revealed that modified MSJZT decreased the mRNA and protein levels of LDH, glutamine synthetase, and PCYT2 in mouse plasma. These results suggested that the mechanisms underlying the anti-GC effects of MSJZT were at least partially mediated by regulating GC-induced energy metabolism dysfunction, such as amino acid, glycolysis, and lipid metabolism (Nie et al, 2019).…”

Protein Phosphatase 1 Regulatory Subunit 3: A Prognostic Biomarker in Stomach Adenocarcinoma

“… 28 A defect in lipid metabolism, for instance, may affect the proliferation and differentiation of tumour cells and may accelerate the occurrence and development of a range of cancer types. 29 In fact, a decrease in choline and cholesterol levels in the serum and tissues of patients with STAD can be employed as a biomarker for the early diagnosis of STAD. 30–32 These findings highlight the importance of defects in lipid metabolism and in cell membrane biosynthesis with respect to cancer progression.…”

Studies on effect of Tongfengxiaofang in HUM model mice using a UPLC–ESI–Q‐TOF/MS metabolomic approach

“…The metabolites with both VIP > 1 and P < 0.05 were selected as the metabolites with significant differences. Accurate mass number matching (tolerance < 25 ppm) was used for identification of the metabolites and secondary spectrum matching and the laboratory self-built database was searched (Nie et al, 2019;. Finally, we analyzed the correlation of significant differences in metabolites in order to further understand the relationships between metabolites in the process of biological state changes.…”