Abstract

UNRAVELING THE POTENCY AND MECHANISMS OF 'TENG QI' FORMULA FOR BREAST CANCER BONE METASTASIS TREATMENT: AN INTEGRATIVE NETWORK PHARMACOLOGY APPROACH

Kumar Ganesan#, Feng Zhang#, Qiaobo Ye, Zhen Ye, Kunhua Wei, Luling Wang, Jianming Wu, Yongxiang Gao, Jianping Chen*

ABSTRACT

According to recent statistics, breast cancer (BC) has had the highest incidence of newly diagnosed cases worldwide since 2020. Distant metastasis is the primary cause of mortality in BC patients, with bone being the most common BC metastatic site. Unfortunately, there are limited medications available for managing breast cancer bone metastasis (BCBM), and most treatments are palliative. This study aims to investigate the efficacy and mechanism of the Teng Qi Formula in treating bone metastasis in breast cancer. MTS assay and colony formation assay were performed to determine the cytotoxicity of the Teng Qi formula in vitro. The xenograft model was employed to determine the tumor growth inhibition effects of the Teng Qi formula in vivo. A wound healing assay was used to analyze the inhibitory effects of the Teng Qi formula on tumor cell motility. Network pharmacological analysis and western blotting assay were used to explore the underlying mechanisms of the Teng Qi formula's efficacy. Although the Teng Qi formula did not significantly contribute to anti-TNBC cell proliferation and viability, it has been demonstrated that its treatment is significantly associated with the inhibition of tumor cell motility, an extended overall survival time, and bone protection in mice with BCBM. Network pharmacological analysis and western blot were employed to uncover the underlying mechanisms of the Teng Qi formula and its anti-BCBM effects. The "Teng Qi" formula regulates approximately 24 distinct signaling pathways enriched by two different strategies during BCBM treatment. Based on the Western blotting assay, the Teng Qi formula is suggested to prevent EMT, independent of the GSK3β pathways. Teng Qi formula exhibits notable inhibitory effects on tumor cell motility and demonstrates beneficial outcomes such as prolonged overall survival in mice with BCBM. It inhibits the EMT independent of GSK3β pathways makes it beneficial in the treatment of BCBM. In addition, integrated network pharmacological analyses suggest that the regulation of 24 different signaling pathways may be the underlying mechanism of the Teng Qi formula in preventing BCBM. These findings highlight the potential of the Teng Qi formula as a therapeutic option for managing BCBM and provide a foundation for further research and development of this herbal medicine in BC treatment.

Keywords: Breast cancer bone metastasis; Teng Qi formula; Network pharmacology; Epithelial-Mesenchymal Transition.