Key Takeaways & Executive Findings
- ā¢ā¢ SYF, a traditional Chinese medicine decoction, significantly inhibits TNBC cell proliferation, migration, and invasion in vitro and suppresses tumor growth and lung metastasis in a xenograft mouse model. ā¢ Network pharmacology and molecular docking identified quercetin and luteolin as key active ingredients that bind to targets KDR1, PPARG, SOD1, and VCAM1, which are regulated by SYF. ā¢ The study provides a scientific basis for the clinical use of SYF in TNBC treatment, highlighting its potential as an adjunct therapy to reduce recurrence and metastasis. ā¢ The integrated approach combining network pharmacology, molecular docking, and experimental validation offers a robust methodology for exploring the mechanisms of complex TCM formulas.
Abstract
Traditional Chinese medicine (TCM) has been used to treat triple-negative breast cancer (TNBC), a breast cancer subtype with poor prognosis. Clinical studies have verified that the Sanyingfang formula (SYF), a TCM prescription, has obvious effects on inhibiting breast cancer recurrence and metastasis, prolonging patient survival, and reducing clinical symptoms. However, its active ingredients and molecular mechanisms are still unclear. In this study, the active ingredients of each herbal medicine composing SYF and their target proteins are obtained from the Traditional Chinese Medicine Systems Pharmacology database. Breast cancer-related genes are obtained from the GeneCards database. Major targets and pathways related to SYF treatment in breast cancer are identified by analyzing the above data. By conducting molecular docking analysis, we find that the active ingredients quercetin and luteolin bind well to the key targets KDR1, PPARG, SOD1, and VCAM1. In vitro experiments verify that SYF can reduce the proliferation, migration, and invasion ability of TNBC cells. Using a TNBC xenograft mouse model, we show that SYF could delay tumor growth and effectively inhibit the occurrence of breast cancer lung metastasis in vivo. PPARG, SOD1, KDR1, and VCAM1 are all regulated by SYF and may play important roles in SYF-mediated inhibition of TNBC recurrence and metastasis.
1. Introduction
According to the latest global cancer data, the number of new breast cancer cases in 2020 reached 2.26 million. Thus, breast cancer has become the worldās most common cancer [1]. Triple-negative breast cancer (TNBC) is a subtype of breast cancer [2] that has a high rate of recurrence and metastasis, a high degree of malignancy, and a poor prognosis [3]. The combination of traditional surgery, radiotherapy, and chemotherapy remains the main treatment for TNBC because of the lack of targeted therapy. However, severe adverse reactions to chemical drugs limit their further development and application [4,5]. Therefore, identifying more effective treatments for TNBC is urgently needed.
According to traditional Chinese medicine (TCM) theory, the main pathogenesis of breast cancer is believed to be āthe deficiency of spleen and kidney, and the accumulation of phlegm, blood stasis, and poisonā. In general, the TCM āspleenā and ākidneyā systems are dampened, as reflected by weakened immunity and reduced nutrient absorption. Consequently, visceral phlegm/inflammation occurs, which results in blood stasis and sporadic accumulation of impairments. The TCM decoction Sanyinfang (SYF) is based on the treatment principle of āinvigorating the kidney and spleen, resolving phlegm and detoxification, and promoting blood circulationā and is composed of Codonopsis pilosula Nannf., Atractylodes macrocephala Koidz., Poria cocos Wolf., Salviae chinensis Herba., Curcuma phaeocaulis Valeton., Epimedium brevicornu Maxim., Solanum nigrum Linn., Scutellariae Barbatae Herba., and Prunella vulgaris Linn. Clinical studies have proven that SYF can effectively prolong disease-free survival and reduce the invasion and metastasis of TNBC [6].
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Xiaojuan Yang, Feifei Li, Youyang Shi, Yuanyuan Wu, Rui Yang, Xiaofei Liu, Yang Zhang, Guangtao Zhang, Mei Ma, Zhanyang Luo, Xianghui Han, Ying Xie, Sheng Liu (2026). Integrated network pharmacology and experimental verification to explore the potential mechanism of San Ying decoction for treating triple-negative breast cancer. Acta Biochimica et Biophysica Sinica. https://doi.org/10.3724/abbs.2024015
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Frequently Asked Questions
What is San Ying decoction (SYF) and how does it work against triple-negative breast cancer?
San Ying decoction (SYF) is a traditional Chinese medicine formula composed of nine herbs. This study shows that SYF inhibits TNBC cell proliferation, migration, and invasion in vitro and suppresses tumor growth and lung metastasis in a mouse model. Network pharmacology and molecular docking suggest that active compounds like quercetin and luteolin bind to key targets (KDR1, PPARG, SOD1, VCAM1), which are regulated by SYF, thereby exerting anti-cancer effects.
What are the key active ingredients in San Ying decoction identified in this study?
The study identified quercetin and luteolin as key active ingredients in SYF. These flavonoids are found in several herbs of the formula and were shown to bind well to the key targets KDR1, PPARG, SOD1, and VCAM1 via molecular docking analysis.
What experimental models were used to validate the effects of San Ying decoction?
The researchers used in vitro experiments with TNBC cell lines to assess proliferation, migration, and invasion. They also used a TNBC xenograft mouse model to evaluate tumor growth and lung metastasis in vivo.
What is the significance of the network pharmacology approach in this study?
Network pharmacology allowed the researchers to systematically identify the active ingredients of SYF, their target proteins, and the pathways involved in breast cancer treatment. This approach helps to understand the multi-component, multi-target mechanism of TCM formulas, providing a scientific basis for their clinical use.
What are the potential clinical implications of this research?
The findings suggest that SYF could be a promising adjunct therapy for TNBC, potentially reducing recurrence and metastasis. The identified targets and pathways may also serve as biomarkers for patient selection or as targets for drug development.
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