title: Xiaotan Sanjie decoction inhibits angiogenesis in gastric cancer through Interleukin-8-linked regulation of the vascular endothelial growth factor pathway.
abstract: BACKGROUND
  Interleukin-8 (IL-8) as a pro-angiogenic factor is strongly associated with gastric cancer metastasis. Xiaotan Sanjie (XTSJ) decoction is an empirical compound prescription based on the phlegm theory of traditional Chinese medicine. Previous studies have shown that XTSJ decoction decreases IL-8 level and formation of vasculogenic mimicry of gastric cancer.
  
  
  OBJECTIVE
  To investigate the link between Xiaotan Sanjie (XTSJ) decoction and IL-8 regulation in the angiogenesis of gastric cancer.
  
  
  METHODS
  Human umbilical vein endothelial cells (HUVECs) were co-cultured with SGC-7901 human gastric cancer cells and exposed to serum samples containing XTSJ decoction and/or IL-8 (1.0ng/mL). The canalization and migration capacities were evaluated by tube formation and transwell migration assay. Protein (immunofluorescence and Western blot) and mRNA (qPCR) expressions were measured in 24-h-cultured HUVECs for vascular endothelial growth factor-A (VEGF-A), vascular endothelial growth factor receptor (VEGFR)-1, and VEGFR-2.
  
  
  RESULTS
  IL-8 significantly promoted and XTSJ decoction inhibited HUVEC tube formation and migration. Links between IL-8 regulation and XTSJ decoction were found in tube formation and migration assays. IL-8 upregulated and XTSJ decoction downregulated VEGF-A, VEGFR-1, and VEGFR-2 protein levels. XTSJ decoction inhibited IL-8-induced VEGF-A and VEGFR-1 protein expressions. Similarly, IL-8 promoted VEGF-A, VEGFR-1, and VEGFR-2 mRNA levels; however, XTSJ decoction inhibited only VEGF-A mRNA. Interestingly, XTSJ decoction inhibited IL-8-induced VEGFR-1 and VEGFR-2 mRNA expression.
  
  
  CONCLUSIONS
  XTSJ decoction might inhibit angiogenesis in gastric cancer through IL-8-linked regulation of the VEGF pathway.
authors.affiliation: Department of Traditional Chinese Medicine, Shanghai Changzheng Hospital, Second Military Medical University, No. 415 Fengyang Road, Huangpu District, Shanghai 200003, China. Electronic address: shijundoctor@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Traditional Chinese Medicine, Shanghai Changzheng Hospital, Second Military Medical University, No. 415 Fengyang Road, Huangpu District, Shanghai 200003, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Traditional Chinese Medicine, Shanghai Changzheng Hospital, Second Military Medical University, No. 415 Fengyang Road, Huangpu District, Shanghai 200003, China.
authors.forename: Pinkang
authors.initials: P
authors.lastname: Wei
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D018920:Coculture Techniques; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; C508606:CXCL8 protein, human; D004365:Drugs, Chinese Herbal; D016209:Interleukin-8; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C000598250:xiaotan sanjie; C501162:FLT1 protein, human; C000588866:KDR protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Angiogenesis; Gastric cancer; Interleukin-8; Vascular endothelial growth factor pathway; Xiaotan Sanjie decoction