title: Matrine inhibits the adhesion and migration of BCG823 gastric cancer cells by affecting the structure and function of the vasodilator-stimulated phosphoprotein (VASP).
abstract: OBJECTIVE
  Vasodilator-stimulated phosphoprotein (VASP) expression is upregulated in human cancers and correlates with more invasive advanced tumor stages. The aim of this study was to elucidate the mechanisms by which matrine, an alkaloid derived from Sophora species plants, acted on the VASP protein in human gastric cancer cells in vitro.
  
  
  METHODS
  VASP was expressed and purified. Intrinsic fluorescence spectroscopy was used to study the binding of matrine to VASP. CD spectroscopy was used to examine the changes in the VASP protein secondary structure. Human gastric carcinoma cell line BGC823 was tested. Scratch wound and cell adhesion assays were used to detect the cell migration and adhesion, respectively. Real-time PCR and Western blotting assays were used to measure mRNA and protein expression of VASP.
  
  
  RESULTS
  In the fluorescence assay, the dissociation constant for binding of matrine to VASP protein was 0.86 mmol/L, thus the direct binding between the two molecules was weak. However, matrine (50 μg/mL) caused obvious change in the secondary structure of VASP protein shown in CD spectrum. Treatments of BGC823 cells with matrine (50 μg/mL) significantly inhibited the cell migration and adhesion. The alkaloid changed the subcellular distribution of VASP and formation of actin stress fibers in BGC823 cells. The alkaloid caused small but statistically significant decreases in VASP protein expression and phosphorylation, but had no significant effect on VASP mRNA expression.
  
  
  CONCLUSIONS
  Matrine modulates the structure, subcellular distribution, expression and phosphorylation of VASP in human gastric cancer cells, thus inhibiting the cancer cell adhesion and migration.
authors.affiliation: Department of Oncology, Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan 430071, China.
authors.forename: Jing-wei
authors.initials: JW
authors.lastname: Zhang
authors.forename: Ke
authors.initials: K
authors.lastname: Su
authors.forename: Wen-tao
authors.initials: WT
authors.lastname: Shi
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Peng-chao
authors.initials: PC
authors.lastname: Hu
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Wei
authors.forename: Jin
authors.initials: J
authors.lastname: Xiang
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
mesh_terms: D000470:Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000502:physiology*; D045744:Cell Line, Tumor; D002464:Cell Migration Inhibition / Q000187:drug effects* / Q000502:physiology*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000502:physiology*; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D017433:Protein Structure, Secondary / Q000187:drug effects / Q000502:physiology; D011807:Quinolizines / Q000494:pharmacology* / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D000093842:Matrines; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D000470:Alkaloids; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D011807:Quinolizines; D000098662:Vasodilator-Stimulated Phosphoprotein; D000093842:Matrines