title: Shikonin inhibits the cell viability, adhesion, invasion and migration of the human gastric cancer cell line MGC-803 via the Toll-like receptor 2/nuclear factor-kappa B pathway.
abstract: OBJECTIVE
  Shikonin is an active naphthoquinone pigment isolated from the root of Lithospermum erythrorhizon. This study was designed to explore the inhibition of Shikonin on cell viability, adhesion, migration and invasion ability of gastric cancer (GC) and its possible mechanism.
  
  
  METHODS
  3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed for cell viability and adhesion ability of MGC-803 cells. Cell scratch repair experiments were conducted for the determination of migration ability while transwell assay for cell invasion ability. Western blot analysis and real-time polymerase chain reaction assay were used for the detection of protein and mRNA expressions.
  
  
  RESULTS
  Fifty per cent inhibitory concentration of Shikonin on MGC-803 cells was 1.854 μm. Shikonin (1 μm) inhibited significantly the adhesion, invasion and migratory ability of MGC-803 cells. Interestingly, Shikonin in the presence or absence of anti-Toll-like receptor 2 (TLR2) antibody (2 μg) and nuclear factor-kappa B (NF-κB) inhibitor MG-132 (10 μm) could decrease these ability of MGC-803 cells markedly, as well as the expression levels of matrix metalloproteinases (MMP)-2, MMP-7, TLR2 and p65 NF-κB. In addition, the co-incubation of Shikonin and anti-TLR2/MG-132 has a significant stronger activity than anti-TLR2 or MG-132 alone.
  
  
  CONCLUSIONS
  The results indicated that Shikonin could suppress the cell viability, adhesion, invasion and migratory ability of MGC-803 cells through TLR2- or NF-κB-mediated pathway. Our findings provide novel information for the treatment of Shikonin on GC.
authors.affiliation: Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, China.|Department of Pharmacology, Shaanxi University of Chinese Medicine, Xianyang, China.
authors.forename: Ji Ping
authors.initials: JP
authors.lastname: Liu
authors.affiliation: Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, China.
authors.forename: Jun Fei
authors.initials: JF
authors.lastname: Gu
authors.affiliation: Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, China.
authors.forename: Mao Mao
authors.initials: MM
authors.lastname: Zhu
authors.affiliation: Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Cui
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D029684:Lithospermum; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020783:Matrix Metalloproteinase 7 / Q000096:biosynthesis; D016328:NF-kappa B / Q000378:metabolism*; D009285:Naphthoquinones / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D009285:Naphthoquinones; D051195:Toll-Like Receptor 2; C016101:shikonin; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2
keywords: Shikonin; gastric cancer; invasion; migratory; toll-like receptor-2