The unduced effect of arsenic trioxide in different types of neuroblastoma cell lines

Abstract

Objective To identify the effect of arsenic trioxide (As2O3) on the differentiation and apoptosis of different types of neuroblastoma(NB) cell lines. Methods The cell lines [SK-N-SH, SK-N-BE2, SH-SY5Y] were induced with different concentrations (0 μmol/L, 1 μmol/L, 3 μmol/L, 5 μmol/L and 7 μmol/L) of arsenic trioxide for 24 h, 48 h, 72 h under the same conditions.The expression of MYCN gene was examined by fluorescence in situ hybridization assay in SK-N-BE2, cell proliferation, cell cycle and cell apoptosis were detected with cell counting kit-8(CCK-8) assay and flow cytometry. Results 5 μmol/L of As2O3 inhibited the expression of MYCN gene in SK-N-BE2; CCK-8 assay indicated that As2O3 inhibited the proliferation of NB cell in a dose-and time-depen-dent manner, the cell proliferation was significantly suppressed compared with the low concentration (1 μmol/L) after treated with As2O3 by 1 μmol/L, 3 μmol/L, 5 μmol/L and 7 μmol/L in 24 h, 48 h and 72 h, SH-SY5Y: 24 h(chisq=9.666 7, P<0.05), 48 h(chisq=9.666 7, P<0.05), 72 h(chisq=9.512 8, P<0.05); SK-N-SH, 24 h(chisq=10.38, P<0.054 6), 48 h(chisq=8.641 0, P<0.05), 72 h(chisq=9.461 5, P<0.05); SK-N-BE2: 24 h(chisq=8.435 9, P<0.05), 48 h(chisq=8.641 0, P<0.05), 72 h(chisq=9.545 5, P<0.05); compared with the control group, the As2O3-treated cells showed increased apoptosis percentage, with the percentage of 1.6%(0 μmol/L), 3.8%(1 μmol/L), 6.1% (3 μmol/L), 10.4%(5 μmol/L), 40.2%(7 μmol/L); the cell cycle was arrested at G2/M phase, which prevented cell division. Conclusions (1)As2O3 play an important role on the NB cells proliferation, apoptosis which were dose-and time-dependent manner.(2)As2O3 can inhibit the expression of MYCN gene.(3)As2O3 also could block NB cell cycle at S and G2/M, and inhibit the cell nucleus replication and the As2O3 had different induced effect between different types of NB cell. Key words: Neuroblastoma; Arsenic trioxide; Cell cycle; MYCN gene