title: Effect on cell cycle progression by N-Myc knockdown in SK-N-BE(2) neuroblastoma cell line and cytotoxicity with STI-571 compound.
abstract: OBJECTIVE
  Neuroblastoma is a common tumor in childhood, and generally exhibits heterogeneity and a malignant progression. MYCN expression and amplification profiles frequently correlate with therapeutic prognosis. Although it has been reported that MYCN silencing causes differentiation and apoptosis in human neuroblastoma cells, MYCN expression influences the cytotoxic potential of chemotherapeutic drugs via the deregulation of the cell cycle. STI-571 may constitute a promising therapeutic agent against neuroblastoma, particularly in cases in which c-Kit is expressed preferentially in MYCN-amplified neuroblastoma.
  
  
  METHODS
  To determine whether STI-571 exerts a synergistic effect on cytotoxicity with MYCN expression, we assessed apoptotic cell death and cell cycle distribution after 72 h of exposure to STI-571 with or with out treatment of SK-N-BE(2) neuroblastoma cells with MYCN siRNA.
  
  
  RESULTS
  MYCN siRNA-treated SK-N-BE(2) cells did not affect apoptosis and cells were arrested in G0/G1 phase after STI-571 treatment.
  
  
  CONCLUSIONS
  siRNA therapy targeted to MYCN may not be effective when administered in combination with STI-571 treatment in cases of neuroblastoma. Therefore, chemotherapeutic drugs that target S or G2-M phase may prove ineffective when applied to cells arrested in the G0/1 phase as the result of MYCN knockdown and STI-571 treatment.
authors.affiliation: Department of Microbiology, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Un-Young
authors.initials: UY
authors.lastname: Yu
authors.forename: Je-Eun
authors.initials: JE
authors.lastname: Cha
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Ju
authors.forename: Kyung-Ah
authors.initials: KA
authors.lastname: Cho
authors.forename: Eun-Sun
authors.initials: ES
authors.lastname: Yoo
authors.forename: Kyung-Ha
authors.initials: KH
authors.lastname: Ryu
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Woo
references.citation: Cancer Lett. 2004 Feb 20;204(2):179-87
references.pmid: 15013217
references.citation: Curr Cancer Drug Targets. 2005 Jun;5(4):273-83
references.pmid: 15975048
references.citation: J Clin Oncol. 2002 Jan 1;20(1):325-34
references.pmid: 11773186
references.citation: Semin Cancer Biol. 2006 Aug;16(4):275-87
references.pmid: 16945552
references.citation: Cancer Res. 1984 Nov;44(11):5444-9
references.pmid: 6488196
references.citation: N Engl J Med. 2005 Jul 14;353(2):172-87
references.pmid: 16014887
references.citation: Biochem Biophys Res Commun. 2006 Dec 8;351(1):192-7
references.pmid: 17055458
references.citation: Nature. 1983 Sep 15-21;305(5931):245-8
references.pmid: 6888561
references.citation: Cancer Lett. 2007 May 18;250(1):17-24
references.pmid: 17141950
references.citation: Int J Cancer. 2003 Aug 20;106(2):147-52
references.pmid: 12800187
references.citation: J Pharmacol Exp Ther. 2000 Oct;295(1):139-45
references.pmid: 10991971