CAJ | 학술논문

目的探讨尿多酸肽(CDA-Ⅱ)单独和联合环腺苷酸(cAMP)对维甲酸耐药的急性早幼粒细胞白血病(APL)细胞的作用.方法以维甲酸耐药的APL细胞株NB4-R2为体外模型,观察使用CDA-Ⅱ单独和联合cAMP处理前后细胞生长和形态的改变;同时利用流式细胞术检测细胞的凋亡特征,包括细胞内DNA含量的分布、亚二倍体(sub-G1)细胞群所占比例、凋亡相关蛋白Bcl-2的表达水平等;并通过电泳鉴定因基因组DNA非随机性降解导致的梯状DNA.结果 CDA-Ⅱ可以通过降低细胞内抗凋亡蛋白Bcl-2的水平,诱导NB4-R2细胞发生凋亡;cAMP则能显著加强CDA-Ⅱ的这一促凋亡作用1 g/L CDA-Ⅱ联合100 μmol/L cAMP共同处理NB4-R2细胞48 h和72 h时Bcl-2阳性细胞比例分别下降至(15.1±4.8)%和(7.3±2.9)%.100 μmol/L cAMP单独作用可使MB4-R2细胞的Bcl-2阳性率由(92.0±0.6)%下降至(75.3±2.0)%.结论尿多酸肽CDA-Ⅱ联合cAMP对于维甲酸耐药的APL细胞株具有强烈的诱导凋亡效应.
목적 탐토뇨다산태(CDA-Ⅱ)단독화연합배선감산(cAMP)대유갑산내약적급성조유립세포백혈병(APL)세포적작용.방법 이유갑산내약적APL세포주NB4-R2위체외모형,관찰사용CDA-Ⅱ단독화연합cAMP처리전후세포생장화형태적개변;동시이용류식세포술검측세포적조망특정,포괄세포내DNA함량적분포、아이배체(sub-G1)세포군소점비례、조망상관단백Bcl-2적표체수평등;병통과전영감정인기인조DNA비수궤성강해도치적제상DNA.결과 CDA-Ⅱ가이통과강저세포내항조망단백Bcl-2적수평,유도NB4-R2세포발생조망;cAMP칙능현저가강CDA-Ⅱ적저일촉조망작용1 g/L CDA-Ⅱ연합100 μmol/L cAMP공동처리NB4-R2세포48 h화72 h시Bcl-2양성세포비례분별하강지(15.1±4.8)%화(7.3±2.9)%.100 μmol/L cAMP단독작용가사MB4-R2세포적Bcl-2양성솔유(92.0±0.6)%하강지(75.3±2.0)%.결론 뇨다산태CDA-Ⅱ연합cAMP대우유갑산내약적APL세포주구유강렬적유도조망효응.
Objective To investigate the effects of CDA-Ⅱ alone or combined with cAMP on the ret-inoic acid (RA)-resistant acute promyelocytic leukemia (APL) cells. Methods The RA-resistant cell line NB4-R2 was used as an in vitro model and treated with CDA-Ⅱ alone or in combination with cAMP. Cell ap-optosis was assessed by morphology observation, distribution of cellular DNA contents and sub-G1 cell popula-tion. The level of Bcl-2 was detected by flow cytometry, DNA "ladder" was detected by agarose-electrophore-sis. Results CDA-Ⅱ could induce NB4-R2 cell apoptosis through decreasing the level of cellular anti-apop-totic protein Bcl-2. cAMP could significantly enhance the role of CDA-Ⅱ. Bcl-2 positive cell rates decreased to (15.1±4.8)% and (7.3±2.9)% in NB4-R2 cells treated with 1 mg/ml CDA-Ⅱ plus 100 μmol/L cAMP for 48 h and 72 h, respectively. While 100μmol/L of cAMP could decrease Bcl-2 positive NB4-R2 cells from (92.0±0.6) % to (75.3±2.0) %. Conclusions CDA-Ⅱ combined with cAMP could exert po-tent apoptotic effect on RA-resistant APL cells.