title: Celastrol induces apoptosis of gastric cancer cells by miR-21 inhibiting PI3K/Akt-NF-κB signaling pathway.
abstract: OBJECTIVE
  Celastrol, a plant triterpene, has anticancer effects by increase of apoptosis. In the present study, the mechanism of celastrol on gastric cancer cell apoptosis was examined.
  
  
  METHODS
  The effect of celastrol on PI3K/Akt and the NF-κB signaling pathway was evaluated with Western blot and luciferase reporter assay. miR-21 expression was determined using real-time PCR. miR-21 inhibitor and miR-21 mimic were used to downregulate and upregulate miR-21 expression, respectively.
  
  
  RESULTS
  It was identified that celastrol was capable of inducing apoptosis of gastric cancer cells, which was mediated via inhibiting the activation of PI3K/Akt and NF-κB. A strong activator of Akt, IGF-1 restored NF-κB activity in cells treated with celastrol. Celastrol could also significantly suppress miR-21 expression. Furthermore, miR-21 inhibitor could decrease phospho-Akt expression and NF-κB activity. Notably, upregulation of miR-21 expression can increase PI3K/Akt and NF-κB activity and decrease apoptosis of gastric cancer cells treated with celastrol, which could be reversed by PI3K inhibitor.
  
  
  CONCLUSIONS
  Our data revealed that the effect of celastrol on apoptosis was due to miR-21 inhibiting the PI3K/Akt-dependent NF-κB pathway.
authors.affiliation: Institute of Clinical Medicine, Taizhou People's Hospital, Nantong University of Medicine, Taizhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Sha
authors.forename: Jun
authors.initials: J
authors.lastname: Ye
authors.forename: Li-xin
authors.initials: LX
authors.lastname: Zhang
authors.forename: Zheng-yun
authors.initials: ZY
authors.lastname: Luan
authors.forename: Ya-bao
authors.initials: YB
authors.lastname: Chen
authors.forename: Jun-xing
authors.initials: JX
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000378:metabolism*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D053148:Caspase 3; D035683:MicroRNAs; D016328:NF-kappa B; D053978:Pentacyclic Triterpenes; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D014315:Triterpenes; C524940:MIRN21 microRNA, human; C050414:celastrol