title: [Inhibitory effect of siRNA targeting ADAM17 on the proliferation of prostate cancer PC-3 cells].
abstract: OBJECTIVE
  To study the effect of siRNA targeting ADAM17 (ADAM17-siRNA) on the proliferation of prostate cancer PC-3 cells.
  
  
  METHODS
  After transfecting PC-3 cells with ADAM17-siRNA 1 and ADAM17-siRNA 2, we detected the expressions of ADAM17 mRNA and protein by RT- PCR and Western blotting, respectively. We measured the changes in the proliferation and DNA synthesis of PC-3 cells by MTT and bromodeoxyuridine (BrdU) incorporation assay, examined the cell cycle profile by flow cytometry, and determined the expressions of the genes associated with PC-3 cell proliferation by Western blotting.
  
  
  RESULTS
  Both ADAM17-siRNA 1 and 2 effectively reduced the expressions of ADAM17 mRNA and protein in the PC-3 cells. Knockdown of ADAM17 with the two siRNAs significantly inhibited cell proliferation as compared with the control group (0.43 +/- 0.57 and 0.44 +/- 0.64 vs 0.80 +/- 0.51, P < 0.05) and down-regulated DNA synthesis (0.48 +/- 0.43 and 0.54 +/- 0.59 vs 0.79 +/- 0.72, P < 0.05). The cell cycle profile showed that the cell population of the G1 phase was markedly higher in both the ADAM17-siRNA groups than in the control ([61.83 +/- 2.41]% and [59.78 +/- 1.92]% vs [41.38 +/- 1.53]%, P < 0.05), but that of the S phase remarkably lower in the former two than in the latter ([23.64 +/- 2.56]% and [25.24 +/- 1.86]% vs [33.51 +/- 1.47]%, P < 0.05), with a concomitant decrease in the expression of the cell cycle protein cyclin D1 and increase in the cyclin-dependent kinase inhibitor p21.
  
  
  CONCLUSIONS
  ADAM17-siRNA can effectively inhibit the proliferation of PC-3 cells by up-regulating cyclin D1 and down-regulating p21 protein, and ADAM17 has a potential value in the gene therapy of prostate cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
authors.forename: Ping
authors.initials: P
authors.lastname: Lin
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Zi-Jun
authors.initials: ZJ
authors.lastname: Liu
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Zou
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xue-Fei
authors.initials: XF
authors.lastname: Zhao
authors.forename: Jin-Liang
authors.initials: JL
authors.lastname: Feng
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Yu
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000072198:ADAM17 Protein; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D015398:Signal Transduction; D014162:Transfection
chemical_list: C530104:CCND1 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019938:Cyclin D1; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human