Wang Jiyan, Chang Hongkai, Su Meng, Zhao Huifang, Qiao Yaya, Wang Yu, Shang Luqing, Shan Changliang, Zhang Shuai
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.
School of Life Science and Bio-Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, China.
Front Pharmacol. 2022 Jun 23;13:934729. doi: 10.3389/fphar.2022.934729. eCollection 2022.
Network pharmacology, as a novel way using bioinformatics to explore drug targets and interactions in cancer, broadens our understanding of drug action, thereby facilitating drug discovery. Here, we utilized network pharmacology to explore the role and mechanism by which cinobufotalin functions in colon adenocarcinoma (COAD). We found that cinobufotalin represses the growth and proliferation of colon cancer cells, and integrated public databases for targets reported to be associated with COAD, together with those predicted to be targets of cinobufotalin. Targets overlapped between COAD-associated proteins and cinobufotalin target proteins were used to filter candidate targets of cinobufotalin in COAD. The following proteins were thought to occupy a key position in COAD-cinobufotalin target networks: SRC, PIK3R1, MAPK1, PIK3CA, HSP90AA1, CTNNB1, GRB2, RHO1, PTPN11, and EGFR. The networks regulated by cinobufotalin were involved mainly in extracellular signal stimulation and transduction, including MAPK signaling pathway, PI3K-AKT signaling pathway, and JAK-STAT signaling pathway. Besides, transcriptome sequencing results also indicated that cinobufotalin inhibits the response of colon cancer cells to extracellular stimulation and promotes cell apoptosis. Molecular docking results showed that cinobufotalin matches in the pocket of the top candidate cinobufotalin target proteins (SRC, PIK3R1, MAPK1 and PIK3CA). These findings demonstrate cinobufotalin can be developed as potential anti-cancer therapeutics.
网络药理学作为一种利用生物信息学探索癌症中药物靶点和相互作用的新方法，拓宽了我们对药物作用的理解，从而促进了药物发现。在此，我们利用网络药理学来探究华蟾酥毒基在结肠腺癌（COAD）中的作用及机制。我们发现华蟾酥毒基可抑制结肠癌细胞的生长和增殖，并整合了与COAD相关的已报道靶点的公共数据库以及那些预测为华蟾酥毒基靶点的数据库。COAD相关蛋白和华蟾酥毒基靶蛋白之间重叠的靶点被用于筛选华蟾酥毒基在COAD中的候选靶点。以下蛋白被认为在COAD-华蟾酥毒基靶标网络中占据关键位置：SRC、PIK3R1、MAPK1、PIK3CA、HSP90AA1、CTNNB1、GRB2、RHO1、PTPN11和EGFR。华蟾酥毒基调控的网络主要涉及细胞外信号刺激和转导，包括MAPK信号通路、PI3K-AKT信号通路和JAK-STAT信号通路。此外，转录组测序结果还表明华蟾酥毒基抑制结肠癌细胞对细胞外刺激的反应并促进细胞凋亡。分子对接结果显示华蟾酥毒基与顶级候选华蟾酥毒基靶蛋白（SRC、PIK3R1、MAPK1和PIK3CA）的口袋匹配。这些发现表明华蟾酥毒基可被开发为潜在的抗癌治疗药物。
