CCAAT增强子结合蛋白同源蛋白在丹参酮ⅡA诱导急性早幼粒细胞白血病细胞分化中的作用

Effect of CCAAT/enhancer-binding protein homologeus protein on differentiation in Tan Ⅱ A induced acute promyelocytic leukemia cells

目的 探索CCAAT增强子结合蛋白同源蛋白（CHOP）在丹参酮ⅡA（TanⅡA）诱导急性早幼粒细胞白血病（APL）细胞分化中的作用。方法 反转录-聚合酶链反应（RT-PCR）及Western blot测定TanⅡA干预的NB4细胞的CHOP表达，通过形态学和膜表面标志检测APL细胞的分化，RNA干扰抑制CHOP表达。结果 TanⅡA诱导APL分化过程中伴有CHOP蛋白表达（1.933±0.987）和mRNA表达（1.587±0.815）的增加，相对于对照组蛋白和mRNA表达（0.537±0.110和0.713±0.090），差异有统计学意义（mRNA水平F＝52.256，P＜0.01；蛋白水平F＝114.852，P＜0.01）；TanⅡA联合RNA干扰抑制CHOP的表达能更加有效的提高APL的分化[（50.767±1.241）% 与（16.167±2.122）%]（F＝989.431，P＜0.05）和凋亡[（89.233±5.581）%与（27.433±2.957）%]（F＝308.961，P＜0.05）。结论 CHOP在TanⅡA诱导APL分化过程中起着负向调节作用，抑制CHOP表达联合TanⅡA可能成为一个更好的治疗策略。

Objective To investigate the effect of CCAAT/enhancer-binding protein homologeus protein （CHOP） in TanⅡA treated acute promyelocytic leukemia （APL） cells. Methods APL cell differentiation was monitored by morphology and membrane differentiation antigens; expression of CHOP was inhibited by siCHOP; mRNA and protein expression of CHOP in TanⅡA-intervened APL cells were examined by RT-PCR and Western blot. Results Expression of CHOP was increased in TanⅡA induced differentiated APL cells （proteins levels 1.933±0.987 vs 0.537±0.110, F = 114.852, P 〈 0.01, mNRA levels 1.587±0.815 vs 0.713±0.090, F = 52.256, P 〈 0.01）, combination of CHOP gene silencing with TanⅡA treatment induced strong APL cell differentiation [（50.767±1.241） % vs （16.167±2.122） %, F = 989.431, P 〈 0.05] and apoptosis [（89.233±5.581） % vs （27.433±2.957） %, F = 308.961, P 〈 0.05]. Conclusion CHOP acts as a negative regulator in TanⅡA induced differentiation. Inhibition of CHOP may be a promising therapeutic strategy.