title: [Anti-leukemia effect of oridonin on Ph(+) acute lymphoblastic leukemia cell SUP-B15].
abstract: OBJECTIVE
  To investigate the anti-leukemia effect of oridonin on Ph(+) acute lymphoblastic leukemia (ALL) cell line SUP-B15.
  
  
  METHODS
  Human Ph(+) ALL cell line was cultured in vitro. The 50% inhibition concentration (IC(50)) of oridonin against SUP-B15 cell line was examined using modified MTT assay. The cellular morphologic changes were observed using a light microscope. The percent of apoptosis of SUP-B15 cell line after drug treatment was evaluated by flow cytometric analysis. The active levels of ABL kinase and its downstream Akt/mTOR, Raf/MEK/ERK, STAT5 signaling pathways and the expression levels of Bcl-2 and BAX were examined by Western blot.
  
  
  RESULTS
  Oridonin inhibited the growth of SUP-B15 cell line in both time- and dose-dependent manner with the IC(50) of oridonin as (7.08 ± 1.21) µmol/L after 72 h treatment. The cellular membrane of SUP-B15 cell line treated with oridonin became unsharp, some of them disintegrated. Oridonin induced apoptosis in SUP-B15 cell line with the apoptosis rates following 0, 5, 10 µmol/L oridonin treatment for 24 h were (6.67 ± 0.83)%, (18.30 ± 1.79)% and (37.63 ± 7.12)%, respectively. Oridonin inhibited activation of ABL kinase and its downstream Akt/mTOR, Raf/MEK/ERK and STAT5 signaling pathways, which were constitutively activated in SUP-B15 cell line, down-regulated the level of anti- apoptotic protein Bcl-2 and up-regulated the expression of pro-apoptotic protein Bax.
  
  
  CONCLUSIONS
  Oridonin exerted anti-leukemia effect in Ph(+)ALL cell line SUP-B15 by inhibiting the activation of ABL kinase and its downstream Akt/mTOR, Raf/MEK/ERK and STAT5 signaling pathways, down-regulating the expression of Bcl-2 and up-regulating the expression of BAX.
authors.affiliation: Department of Hematology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Guo
authors.forename: Qing-qing
authors.initials: QQ
authors.lastname: Shan
authors.forename: Yu-ping
authors.initials: YP
authors.lastname: Gong
authors.forename: Juan
authors.initials: J
authors.lastname: Lin
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.forename: Rui-qing
authors.initials: RQ
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction
chemical_list: D045786:Diterpenes, Kaurane; C011959:oridonin