title: Pseudolaric acid B inhibits gastric cancer cell metastasis in vitro and in haematogenous dissemination model through PI3K/AKT, ERK1/2 and mitochondria-mediated apoptosis pathways.
abstract: Pseudolaric acid B (PAB) is the major bioactive constituent in the root bark of Pseudolarix kaempferi and has been reported to have cytotoxicity against tumor cells. Our in vivo experiments showed that PAB could inhibit gastric cancer cell lung metastasis in a nude mouse haematogenous dissemination model. To evaluate the anti-metastasis mechanism of PAB in gastric cancer cells, cytological experiments were performed. The results showed that PAB could inhibit the adhesion ability to matrigel, migration, invasion and colony formation ability of BGC-823 and MKN-45 cells. Western blot further confirmed that the inhibitory effects of PAB on anti-metastasis may involve regulating the expression of the metastasis-related proteins MMP-9, HIF-1α, VEGF, VEGFR2, E-Cadherin and Ezrin. We obtained further proof that PAB which could be used as a multi-targeted agent to inhibit the PI3K/AKT, ERK1/2 and mitochondria-mediated apoptosis pathways and consequently suppress tumor growth and metastasis. Our experiments suggest that PAB-induced effects may have novel therapeutic applications for the treatment of gastric cancer.
authors.affiliation: Department of Gastrointestinal Tumor Pathology of Cancer Institute and General Surgery Institute, The First Hospital of China Medical University, Shenyang, China; Colledge of Pharmacy, Liaoning University, Shenyang, China. Electronic address: wangdan@lnu.edu.cn.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Tumor Pathology of Cancer Institute and General Surgery Institute, The First Hospital of China Medical University, Shenyang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xin
authors.affiliation: Colledge of Life Science, Liaoning University, Shenyang, China.
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Gastrointestinal Tumor Pathology of Cancer Institute and General Surgery Institute, The First Hospital of China Medical University, Shenyang, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Tumor Pathology of Cancer Institute and General Surgery Institute, The First Hospital of China Medical University, Shenyang, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Sun
authors.affiliation: Laboratory Animal Center, China Medical University, Shenyang, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D004224:Diterpenes / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D004224:Diterpenes; D012333:RNA, Messenger; C058391:pseudolaric acid B; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: ERK1/2; Gastric cancer; Metastasis; Mitochondria-mediated apoptosis pathway; PI3K/AKT; Pseudolaric acid B