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.
Highlights
Gastric cancer (GC) is the fourth most common cancer and the second-leading cause of cancer death worldwide [1]
These results indicate that the quality of modified Si Jun Zi Tang (MSJZT) was controlled, and the extraction method was stable and reliable
MSJZT remarkably reduce the expression of lactic dehydrogenase (LDH), glutamine synthetase (GS), and PCYT2 both in mRNA and protein level. These results revealed that MSJZT have the ability to rectify glycolytic, amino acid, and phospholipids metabolism in GC
Summary
Gastric cancer (GC) is the fourth most common cancer and the second-leading cause of cancer death worldwide [1]. This famous SJZT formula was first listed in the classical medical book “Tai-Ping-HuiMin-He-Ji-Ju-Fang” during the Song dynasty. Metabolomics focuses on changes in the overall terminal products, which is consistent with the overall concept of TCM [15,16,17]. In recent years, it has become a promising technology in the study of human cancers and has been successfully applied in various cancers, such as stomach, colorectal, and pancreatic cancer [18,19,20]. In this study, a hydrophilic interaction liquid chromatography and liquid chromatography quadrupole time-of-flight mass spectrometry (HILIC UHPLC-Q-TOF/ MS)-based metabolomics approach was used as an exploration analysis platform to capture the altered endogenous metabolites in the plasma of GC tumour-bearing nude mice and illuminate the antitumour effects and mechanisms of MSJZT
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