Effect on cell cycle progression by N-Myc knockdown in SK-N-BE(2) neuroblastoma cell line and cytotoxicity with STI-571 compound.
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.
Yu
Un-Young
UY
Department of Microbiology, Ewha Womans University School of Medicine, Seoul, Korea.
Cha
Je-Eun
JE
Ju
Sun-Young
SY
Cho
Kyung-Ah
KA
Yoo
Eun-Sun
ES
Ryu
Kyung-Ha
KH
Woo
So-Youn
SY
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