A Network Pharmacological Elucidation of the Systematic Treatment Activities and Mechanisms of the Herbal Drug FDY003 Against Esophageal Cancer

Abstract

Despite accumulating evidence for the value of herbal drugs for cancer treatment, the mechanisms underlying their effects have not been fully elucidated in a systematic manner. In this study, we performed a network pharmacological analysis to elucidate the anti-esophageal cancer (EC) properties of the herbal drug FDY003, a mixture of Artemisia capillaris Thunberg (AcT), Cordyceps militaris (Linnaeus) Link (Cm), and Lonicera japonica Thunberg (LjT). FDY003 reduced human EC cell viability and increased the pharmacological effects of chemotherapeutic drugs. There were 15 active pharmacological chemicals targeting 61 EC-associated genes and proteins in FDY003. The FDY003 targets were key regulators of major oncogenic EC-associated signaling pathways, such as phosphoinositide 3-kinase (PI3K)-Akt, hypoxia-inducible factor (HIF)-1, mitogen-activated protein kinase (MAPK), tumor necrosis factor (TNF), p53, Janus kinase (JAK)-signal transducer and activator of transcription (STAT), erythroblastic leukemia viral oncogene homolog (ErbB), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B), and vascular endothelial growth factor (VEGF) cascades. These EC-associated genes, proteins, and pathways targeted by FDY003 determine the malignant behaviors of EC cells, including cell death, survival, division, proliferation, and growth. This network pharmacological analysis provides an integrative view of the mechanisms by which FDY003 contributes to EC treatment.