title: Inhibitory effects of tanshinone II-A on invasion and metastasis of human colon carcinoma cells.
abstract: OBJECTIVE
  To investigate the effects and possible mechanisms of tanshinone II-A, an alcohol extract of the root of Salvia miltiorrhiza Bunge, on tumor invasion and metastasis of human colon carcinoma (CRC) cells.
  
  
  METHODS
  The effects of tanshinone II-A on invasion and metastasis of CRC cell lines HT29 and SW480 were evaluated by in vitro and in vivo assays. Western blotting was used to investigate possible molecular mechanisms of tanshinone II-A anti-cancer actions.
  
  
  RESULTS
  Tanshinone II-A inhibited migration and invasion of CRC cells in a dose-dependent manner. The inhibitory effect also depended on time, with the most significant effects observed at 72 h. Tanshinone II-A also significantly inhibited in vivo metastasis of colon carcinoma SW480 cells. It inhibited in vitro and in vivo invasion and metastasis of CRC cells by reducing levels of urokinase plasminogen activator (uPA) and matrix metalloproteinases (MMP)-2 and MMP-9, and by increasing levels of tissue inhibitor of matrix metalloproteinase protein (TIMP)-1 and TIMP-2. Tanshinone II-A was also shown to suppress the nuclear factor-kappaB (NF-kappaB) signal.
  
  
  CONCLUSIONS
  Tanshinone II-A inhibited in vitro and in vivo invasion and metastasis of CRC cells. The effect resulted from changes in the levels of uPA, MMP-2, MMP-9, TIMP-1 and TIMP-2, and apparent inhibition of the NF-kappaB signal transduction pathway.
authors.affiliation: Department of General Surgery, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China.
authors.forename: Yun-feng
authors.initials: YF
authors.lastname: Shan
authors.forename: Xian
authors.initials: X
authors.lastname: Shen
authors.forename: Yuan-kang
authors.initials: YK
authors.lastname: Xie
authors.forename: Ji-cai
authors.initials: JC
authors.lastname: Chen
authors.forename: Hong-qi
authors.initials: HQ
authors.lastname: Shi
authors.forename: Zheng-ping
authors.initials: ZP
authors.lastname: Yu
authors.forename: Qi-tong
authors.initials: QT
authors.lastname: Song
authors.forename: Men-tao
authors.initials: MT
authors.lastname: Zhou
authors.forename: Qi-yu
authors.initials: QY
authors.lastname: Zhang
mesh_terms: D045784:Abietanes; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009362:Neoplasm Metastasis / Q000517:prevention & control; D010616:Phenanthrenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology; D018517:Plant Roots; D027561:Salvia miltiorrhiza / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D010616:Phenanthrenes; D010936:Plant Extracts; C021751:tanshinone