Therapeutic effects of Euphorbia Pekinensis and Glycyrrhiza glabra on Hepatocellular Carcinoma Ascites Partially Via Regulating the Frk-Arhgdib-Inpp5d-Avpr2-Aqp4 Signal Axis.
To clarify unknown rationalities of herbaceous compatibility of Euphorbia Pekinensis (DJ) and Glycyrrhiza glabra (GC) acting on hepatocellular carcinoma (HCC) ascites, peritoneum transcriptomics profiling of 15 subjects, including normal control (Con), HCC ascites mouse model (Mod), DJ-alone, DJ/GC-synergy and DJ/GC-antagonism treatment groups were performed on OneArray platform, followed by differentially expressed genes (DEGs) screening. DEGs between Mod and Con groups were considered as HCC ascites-related genes, and those among different drug treatment and Mod groups were identified as DJ/GC-combination-related genes. Then, an interaction network of HCC ascites-related gene-DJ/GC combination-related gene-known therapeutic target gene for ascites was constructed. Based on nodes' degree, closeness, betweenness and k-coreness, the Frk-Arhgdib-Inpp5d-Avpr2-Aqp4 axis with highly network topological importance was demonstrated to be a candidate target of DJ/GC combination acting on HCC ascites. Importantly, both qPCR and western blot analyses verified this regulatory effects based on HCC ascites mice in vivo and M-1 collecting duct cells in vitro. Collectively, different combination designs of DJ and GC may lead to synergistic or antagonistic effects on HCC ascites partially via regulating the Frk-Arhgdib-Inpp5d-Avpr2-Aqp4 axis, implying that global gene expression profiling combined with network analysis can offer an effective way to understand pharmacological mechanisms of traditional Chinese medicine prescriptions.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Yanqiong
Y
Zhang
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.|Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Chen
C
Yan
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Yuting
Y
Li
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Xia
X
Mao
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine; Nanjing University of Chinese Medicine, Nanjing 210023, China.
Weiwei
W
Tao
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine; Nanjing University of Chinese Medicine, Nanjing 210023, China.
Yuping
Y
Tang
College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
Ya
Y
Lin
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Qiuyan
Q
Guo
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine; Nanjing University of Chinese Medicine, Nanjing 210023, China.
Jingao
J
Duan
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Na
N
Lin
D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics; D001201:Ascites / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D028481:Euphorbia / Q000737:chemistry*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006035:Glycyrrhiza / Q000737:chemistry*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D015778:Minor Histocompatibility Antigens / Q000235:genetics; D009363:Neoplasm Proteins; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / Q000235:genetics; D010936:Plant Extracts / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases; D017483:Receptors, Vasopressin / Q000235:genetics; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta / Q000235:genetics; D019061:src-Family Kinases / Q000235:genetics
C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; C569659:Arhgdib protein, mouse; D014408:Biomarkers, Tumor; D015778:Minor Histocompatibility Antigens; D009363:Neoplasm Proteins; D010936:Plant Extracts; D017483:Receptors, Vasopressin; D062949:rho Guanine Nucleotide Dissociation Inhibitor beta; D011505:Protein-Tyrosine Kinases; C490512:Frk protein, mouse; D019061:src-Family Kinases; C000606433:Inpp5d protein, mouse; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases