Abstract
Objective To investigate the potential therapy targets and pharmacological mechanism of traditional Chinese medicine (TCM) Xihuang pill in liver cancer based on network pharmacology. Methods Drug ingredients-target network was constructed based on the target sets of Xihuang pill and liver cancer. The overlapping genes between Xihuang pill targets and liver cancer-related molecular targets were investigated using comparative analysis. Moreover, the PPI network and module was constructed based on overlapping genes and hub nodes, respectively, followed by the pathway enrichment analysis. Results A drug ingredients-target network was established with 1184 nodes and 11035 interactions. Moreover, a total of 106 overlapping genes were revealed between drug targets and liver cancer molecular targets. Furthermore, a PPI network and 4 modules were further investigated based on overlapping genes, respectively. These hub nodes such as VEGFA and EGFR were mainly enriched in GO functions including positive regulation of MAP kinase activity, activation of protein kinase activity, regulation of MAP kinase activity, and pathways like proteoglycans in cancer, bladder cancer, and estrogen signaling. Conclusion VEGFA and EGFR might be potential therapy targets of Xihuang pill in liver cancer. Furthermore, the effect of Xihuang pill on liver cancer might be realized by targeting VEGFA and EGFR in pathways like proteoglycans in cancer and estrogen signaling.
Highlights
As the second leading cause of death, liver cancer has caused a wide social burden for a long period of time [1]
Identification of Ingredients of Drug. e chemical ingredients of Xihuang pill were collected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database [13] and the Traditional Chinese Medicine Integrated Database (TCMID, http://www.megabionet.org/tcmid/) [14]
According to the relevant parameters of the pharmacokinetic properties, the ingredients were screened according to oral bioavailability (OB) and drug-likeness (DL) values and those ingredients with DL ≥ 0.18 and OB ≥ 30% were selected as the active ingredients [15, 16]
Summary
As the second leading cause of death, liver cancer has caused a wide social burden for a long period of time [1]. Us, exploring the effective clinical treatment for liver cancer is necessary. Traditional Chinese medicine (TCM) has been widely used for clinical treatment of various tumors such as liver cancer [4, 5]. A previous study shows that Xihuang pill has an anticancer effect on breast tumor [8], gastric cancer, and primary liver cancer [7]. Xihuang pill could improve quality of life and clinical manifestations of advanced primary liver cancer patients [9]. A previous study indicates that there is a reversal effect of serum containing Xihuang pill on the multidrug resistance of liver cancer cells via P-glytoprotein pathway [10]. Xihuang pill is effective in treatment of liver cancer, the drug targets and pharmacological mechanisms of Xihuang pill on liver cancer are still unclear
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