title: [Artemisinin inhibits proliferation of gallbladder cancer cell lines through triggering cell cycle arrest and apoptosis].
abstract: OBJECTIVE
  To evaluate the effects of artemisinin on proliferation, cell cycle and apoptosis of gallbladder cancer cells.
  
  
  METHODS
  Gallbladder carcinoma cell lines(GBC-SD and NOZ)were cultured in vitro. The effects of artemisinin in different concentration on proliferation of the two cell lines in vitro were examined using MTT assay. The cell cycle distribution of GBC-SD and NOZ cells 24 h after treatments with artemisinin(20 μmol/L) were examined using flow cytometry. The apoptosis of GBC-SD and NOZ cells 24 h after treatments with artemisinin (20 μmol/L) were examined using Annexin V/PI staining.The expressions of p-ERK1/2, CDK4, cyclin D1, p16, cytochrome C and caspase-3 were examined by Western blot assay. t-test and one way ANOVA were used to evaluate the differences between two groups and more than two groups, respectively.
  
  
  RESULTS
  The cell proliferation was significantly inhibited by artemisinin, the IC50 of artemisinin against GBC-SD and NOZ cells were 14.05 μmol/L and 12.42 μmol/L, respectively.Artemisinin induced cycle arrest, and G1 population of GBC-SD and NOZ cells increased to 74.60% and 78.86%. Cell apoptosis and apoptotic population of GBC-SD and NOZ cells were increased to 15.67% and 16.51% after dealt with artemisinin, respectively. In addition, expression of p16 was increased, and expressions of p-ERK1/2, CDK4 and cyclin D1 were down-regulated by artemisinin(all P<0.05). Cytochrome C was released from mitochondria to cytoplasm leading to the activation of caspase-3 and PARP after dealt with artemisinin(P<0.05).
  
  
  CONCLUSIONS
  The inhibition effect of artemisinin on the proliferation gallbladder cancer cells is accompanied by down-regulation of ERK1/2 signaling pathway, G1 phase arrest and triggering caspase-3-mediate apoptosis.
authors.affiliation: Department of Oncology Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu 233003, China.
authors.forename: J G
authors.initials: JG
authors.lastname: Jia
authors.forename: L G
authors.initials: LG
authors.lastname: Zhang
authors.forename: C X
authors.initials: CX
authors.lastname: Guo
authors.forename: Y G
authors.initials: YG
authors.lastname: Wang
authors.forename: B L
authors.initials: BL
authors.lastname: Chen
authors.forename: Y M
authors.initials: YM
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Qian
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D037621:Artemisinins / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D005706:Gallbladder Neoplasms / Q000473:pathology*; D006801:Humans; D020935:MAP Kinase Signaling System; D008928:Mitochondria / Q000378:metabolism
chemical_list: D037621:Artemisinins; C530104:CCND1 protein, human; D019938:Cyclin D1; D045304:Cytochromes c; C031327:artemisinin; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; C505407:CASP3 protein, human; D053148:Caspase 3