Mechanism of Marsdenia tenacissima in treating breast cancer by targeting the MAPK signaling pathway: Utilising metabolomics, network pharmacology, and In vivo experiments for verification.

[ETHNOPHARMACOLOGICAL RELEVANCE] Marsdenia tenacissima dried stems have been used to treat asthma, trachitis, rheumatism, and carbuncles. M. Tenacissima extract is now available in China under the brand name "Xiao Ai Ping" and is commonly used in conjunction with chemotherapy to treat a number of diseases, including liver cancer, gastric cancer, colon cancer, and non-small cell lung cancer.

[PURPOSE OF THE STUDY] The research focused on the potential mechanisms contributing to the in vivo therapeutic effects on breast cancer using the ethyl acetate portion of M. tenacissima extract (EMTE), demonstrating significant promise in treating lung cancer in our initial experiments.

[MATERIALS AND METHODS] We examined the impact of EMTE on the growth of breast cancer through experiments on homoplastic breast cancer mice. Moreover, we utilized UPLC-Q-TOF/MS analysis to identify the components of EMTE and anticipate its potential therapeutic targets. Through network pharmacology, we predicted the potential targets and pathways affected by EMTE in relation to breast cancer. Additionally, we analysed the metabolic changes induced by EMTE during its anti-breast cancer effects.

[RESULTS] The MAPK pathway was identified as the most likely route by which EMTE could influence breast cancer through network pharmacological enrichment of pathways. Research on animals showed that EMTE could successfully inhibit the development of breast tumours in the homoplastic breast cancer mouse model. We observed that EMTE treatment affected the metabolism of breast cancer mice, particularly in the biosynthesis of phenylalanine, tyrosine, tryptophan, linoleic acid metabolism, and pyrimidine metabolism. These metabolic alterations may have contributed to the effects of glycolysis, tumour immune evasion, and pyrimidine de novo synthesis.

[CONCLUSION] Based on the results of network pharmacological and metabolomic analysis, we postulate that the inhibition of the MAPK/ERK pathway may have played a role in promoting apoptosis in breast cancer cells and confirmed relevant protein expression of the MAPK/ERK signaling pathway with Western blotting in tumour tissue of homoplastic breast cancer mice.