title: Wogonin, an active ingredient of Chinese herb medicine Scutellaria baicalensis, inhibits the mobility and invasion of human gallbladder carcinoma GBC-SD cells by inducing the expression of maspin.
abstract: BACKGROUND
  A traditional Chinese medicine Scutellaria baicalensis is prescribed for the treatment of a variety of inflammatory diseases and tumors in clinic in China. However, the detailed mechanism of anti-metastasis effect of wogonin, a main active ingredient of Scutellaria baicalensis, remains elusive.
  
  
  OBJECTIVE
  The present study was designed to investigate the action and mechanism of wogonin on the mobility and invasion of human gallbladder carcinoma GBC-SD cells.
  
  
  METHODS
  Viability, apoptosis, mRNA and protein expression of tumor cells were analyzed by MTT, Annexin V staining, real-time PCR and Western blot, respectively. The migration and invasion assay was used to evaluate the anti-metastasis effect of wogonin. Knockdown of maspin was performed by specific small interference RNA.
  
  
  RESULTS
  Wogonin at the dose of 1-10 μM, which did not induce apoptosis, significantly inhibited the mobility and invasion activity of human gallbladder carcinoma GBC-SD cells. In addition, the expressions of matrix metalloproteinase (MMP)-2, MMP-9 and phosphorylated extracellular regulated protein kinase 1/2 (ERK1/2) but not phosphorylated Akt were dramatically suppressed by wogonin in a concentration-dependent manner. Furthermore, the metastasis suppressor maspin was confirmed as the downstream target of wogonin. Both maspin mRNA and protein were upregulated by wogonin. Interestingly, the knockdown of maspin resulted in almost completely blocking of wogonin-induced inhibition of MMP-2, MMP-9 and phosphorylated ERK1/2 as well as the mobility and invasion activity of GBC-SD cells.
  
  
  CONCLUSIONS
  These findings suggest that wogonin inhibits cell mobility and invasion by upregulating the metastasis suppressor maspin. Together, these data provide novel insights into the chemoprotective effect of wogonin, a main active ingredient of Chinese medicine Scutellaria baicalensis.
authors.affiliation: Department of General Surgery, Xinhua Hospital, Affiliated to School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, Shanghai 200092, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Dong
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.forename: Wenguang
authors.initials: W
authors.lastname: Wu
authors.forename: Maolan
authors.initials: M
authors.lastname: Li
authors.forename: Jiahua
authors.initials: J
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Lu
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Mu
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Songgang
authors.initials: S
authors.lastname: Li
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wang
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000302:isolation & purification / Q000494:pharmacology*; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010946:Plants, Medicinal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D031364:Scutellaria baicalensis / Q000737:chemistry; D015843:Serpins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044950:Flavanones; D010936:Plant Extracts; C085344:SERPIN-B5; C499814:Scutellaria baicalensis extract; D015843:Serpins; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C085514:wogonin