Purpose: Network pharmacology has become a powerful means of understanding the mechanisms underlying the action of Chinese herbs in cancer treatment. This study aims to validate the preventive effects and molecular mechanisms of a clinical prescription XIAOPI formula against breast cancer.

Experimental Design: The anti-metastasis ability of XIAOPI was validated by MMTV-PyMT mice and in vitro cell models. A network pharmacology-based method, which combined large-scale text-mining, drug-likeness filtering, target prediction and network analysis, was conducted to predict TAMS/CXCL-1 as key mediator of XIAOPI formula preventing breast cancer metastasis, further supported by cytokine array analysis in vitro and in vivo.

Results: In vivo breast cancer xenograft data showed that XIAOPI delayed breast cancer development and efficiently inhibited lung metastasis, accompanied by prolonged survival benefits and decreased cancer stem cell subpopulations. However, similar phenomenon were not observed in a cell model. The herb-ingredient-target network analysis further identified a total of 81 genes closely correlated with the breast cancer chemoprevention effects of XIAOPI. Cytokine array analysis further validated CXCL-1 as the key target of XIAOPI both in vitro and in vivo. Evaluation of the mechanism demonstrated that CXCL-1 administration significantly abrogated the metastatic inhibition effects of XIAOPI on breast cancer migration, invasion, stem cells subpopulations, epithelial-mesenchymal transition(EMT), or mammosphere formation abilities.

Conclusions: Overall, our study not only provides experimental evidence and molecular mechanisms that may facilitate the safe and effective use of herbal medicine for the prevention of breast cancer growth or metastasis, and may lead to CXCL-1-based therapeutic strategies for mammary malignancies.

Citation Format: Neng Wang, Zhiyu Wang, Yifeng Zheng, Shengqi Wang, Fengxue Zhang, Yi Lin. Integrating network biology and polypharmacology to reveal TAMS/CXCL-1 as key mediator of XIAOPI formula preventing breast cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1311.