title: [Inhibitory effect of Akt inhibitor deguelin on the growth of PC-3 prostate cancer cells].
abstract: OBJECTIVE
  To study the inhibitory effect of Akt inhibitor deguelin on PC-3 human prostate cancer cell lines and its possible mechanism.
  
  
  METHODS
  PC-3 human prostate cancer cells were cultured in deguelin at the concentrations of 10, 100, 500 and 1 000 nmol/L for 24, 48 and 72 hours, respectively. Then the inhibitory effect of deguelin on the proliferation of the PC-3 cells was determined by MTT assay and that on the cell cycle was detected by flow cytometry. The expression levels of MDM2 and GSK3beta mRNA were measured by RT-PCR and those of MDM2 and GSK3beta proteins by Western blot.
  
  
  RESULTS
  At 24, 48 and 72 hours, the inhibition rates of deguelin on the proliferation of the PC-3 prostate cancer cells were (91.10 +/- 3.75), (86.39 +/- 1.16) and (79.51 +/- 2.63)% at 10 nmol/L, (82.46 +/- 3.65), (76.84 +/- 0.97) and (69.69 +/- 2.30) % at 100 nmol/L, (81.46 +/- 0.41), (75.56 +/- 1.12) and (54.07 +/- 3.21)% at 500 nmol/L, and (66.77 +/- 2.82), (58.22 +/- 0.35) and (39.34 +/- 2.40)% at 1000 nmol/L, all with statistically significant differences from the control group (P < 0.01). Deguelin at 10, 100, 500 and 1 000 nmol/L increased the cell cycles blocked in the G0/G1 phase ([62.4 +/- 2.2], [63.6 +/- 1.1 ], [65.0 +/- 0.3] and [66.5 +/- 1.9]%, P < 0.01) and reduced the percentage of the S-phase cells ([14.7 +/- 2.4], [11.1 +/- 5.2], [5.8 +/- 1.1] and [7.0 +/- 0.6]%, P < 0.01). RT-PCR and Western blot showed markedly up-regulated expressions of GSK3 P3 a3beta down-regulated expressions of MDM2 mRNA and proteins in the PC-3 cells treated with deguelin.
  
  
  CONCLUSIONS
  Akt inhibitor deguelin can inhibit the proliferation of PC-3 human prostate cancer cells by affecting the down-stream signal molecules GSK3P3 and betaDM2 in the Akt pathway.
authors.affiliation: Department of Urology, Central Hospital of Enshi Prefecture, Enshi, Hubei 445800, China.
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Chen
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Hu
authors.forename: Ke-Hua
authors.initials: KH
authors.lastname: Jiang
authors.forename: Sheng-Liang
authors.initials: SL
authors.lastname: Zhu
authors.forename: Chun-Xiong
authors.initials: CX
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
authors.forename: Yong
authors.initials: Y
authors.lastname: Lan
authors.forename: Su
authors.initials: S
authors.lastname: Chen
authors.forename: Hong-Gang
authors.initials: HG
authors.lastname: Yuan
authors.forename: Xing-Fu
authors.initials: XF
authors.lastname: Song
authors.forename: Yan-Lin
authors.initials: YL
authors.lastname: Wang
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D012402:Rotenone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D012402:Rotenone; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; C107676:deguelin