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一氧化氮供体型齐墩果烷衍生物对肝癌细胞增殖和凋亡的影响

Effects of NO-donating oleanane derivatives on cell proliferation and apoptosis of human hepatoma cell lines

  • 摘要: 对一氧化氮(NO)供体型齐墩果烷衍生物(SO-10)对肝癌的抑制作用进行了研究。检测了NO在其诱导肝癌细胞凋亡中的作用。MTT法检测显示SO-10能显著抑制肝癌细胞株(HepG2、BEL-7402和SMMC-7721)的增殖,SO-10作用48 h 后的IC50分别为HepG2(1.19±0.12 μmol/L)、BEL-7402 (1.98±0.85 μmol/L) 和SMMC-7721 (5.92±0.58 μmol/L);流式细胞仪检测显示0.5-2 μmol/L的SO-10均诱导肝癌细胞株HepG2凋亡,细胞凋亡率随浓度增加而上升;Griess法显示SO-10作用后HepG2内的NO水平随着药物作用时间的延长而增加,用NO清除剂预处理后,随着NO浓度的降低,SO-10对HepG2细胞增殖的抑制作用也相应降低。提示SO-10对肝癌细胞有抗增殖作用和诱导凋亡作用,可能与SO-10在肝癌细胞中释放NO有关。

     

    Abstract: To investigate the inhibition effects of NO-donating oleanane derivative (SO-10) on human hepatoma cell lines and the antitumor activities of NO, MTT assay was used to analyze human hepatoma cells (HepG2,BEL-7402 and SMMC-7721) proliferation.SO-10 strongly inhibited human hepatoma cell proliferation and their IC50values were 1.19±0.12 μmol/L for HepG2,1.98±0.85 μmol/L for BEL-7402 and 5.92±0.58 μmol/L for SMMC-7721 after 48 h.Apoptosis of HepG2 cells induced by SO-10 was detected by flow cytometry (FCM),showing that SO-10 dramatically triggered apoptosis in HepG2 cells in a dose-dependent manner.The amount of NO produced by SO-10 were increased from 30 min to 6 h examined by the Griess assay.Furthermore,pre-treatment with different concentrations of hemoglobin notably reduced the concentrations of NO and inhibited the cytotoxicity of SO-10 against HepG2 cells.SO-10 showed remarkable effects of inhibiting cell proliferation and inducing apoptosis of human hepatoma cell lines.The significantly high concentrations of NO produced by SO-10 might contribute to its cytotoxicity against HepG2 cells.

     

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