Gui Yu, Dai Yifei, Wang Yumei, Li Shengrong, Xiang Lei, Tang Yuqin, Tan Xue, Pei Tianli, Bao Xilinqiqige, Wang Dong
State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
Comput Struct Biotechnol J. 2022 Jun 26;20:3461-3472. doi: 10.1016/j.csbj.2022.06.044. eCollection 2022.
Taohong Siwu Decoction (TSD), a classical gynecological prescription that was firstly reported 600 years ago, has been widely used in the adjuvant treatment of breast cancer (BRCA) in China. However, the mechanism of action of TSD in treating BRCA has remained unclear. Here, high-throughput sequencing-based high-throughput screening (HTS) technology was used to reveal the molecular mechanism of TSD, combination with bioinformatics and systems pharmacology in this study. Firstly, our results showed that TSD exerts an anticancer effect on BRCA cells by inhibiting cell proliferation, migration and inducing apoptosis as well as cell-cycle arrest. And our results from HTS suggested that herbs of TSD could significantly inhibit KRAS pathway and pathway in cancer, and activate apoptosis pathway, p53 pathway and hypoxia pathway, which may lead to the anticancer function of TSD. Further, we found that TSD clearly regulates and genes, which play an important role in the development and progression of tumor and have significant correlation with overall survival in BRCA patients. By molecular docking, we discovered that Pentagalloylglucose, a compound derived from TSD, might directly bind to and inhibit the function of BRD4, which is a reported transcriptional activator of gene, and thus repress the expression of . Taken together, this study explores the mechanism of TSD in anti-BRCA by combining HTS technology, bioinformatics analysis and systems pharmacology.
桃红四物汤（TSD）是一种600年前首次报道的经典妇科方剂，在中国已被广泛用于乳腺癌（BRCA）的辅助治疗。然而，TSD治疗BRCA的作用机制仍不清楚。在本研究中，采用基于高通量测序的高通量筛选（HTS）技术，并结合生物信息学和系统药理学来揭示TSD的分子机制。首先，我们的结果表明，TSD通过抑制细胞增殖、迁移以及诱导凋亡和细胞周期阻滞，对BRCA细胞发挥抗癌作用。我们高通量筛选的结果表明，TSD中的草药可显著抑制KRAS通路和癌症中的通路，并激活凋亡通路、p53通路和缺氧通路，这可能导致TSD的抗癌功能。此外，我们发现TSD明显调节了在肿瘤发生和发展中起重要作用且与BRCA患者总生存期显著相关的 和 基因。通过分子对接，我们发现TSD中的一种化合物五倍子酰葡萄糖可能直接结合并抑制BRD4的功能，BRD4是一种已报道的 基因转录激活因子，从而抑制 的表达。综上所述，本研究通过结合HTS技术、生物信息学分析和系统药理学，探索了TSD抗BRCA的机制。
