摘要
细胞凋亡机制的探索对于急性早幼粒细胞白血病治疗至关重要。B细胞淋巴瘤-2(B-cell lymphoma-2,Bcl-2)基因家族是调控细胞凋亡的关键基因。拮抗和促进细胞凋亡的动态平衡决定细胞的命运。本研究通过对凋亡相关基因的表达水平与细胞生长趋势的分析表明,高三尖杉酯碱与全反式维甲酸联合处理细胞可以更有效地促进早幼粒细胞凋亡(P<0.05)。随着药物浓度变化,Bcl-2与相关基因的表达呈现先升高后降低的趋势(P<0.05)。低浓度药物处理时,抗凋亡蛋白质Bcl-2表达升高,阻止细胞凋亡(P<0.05)。随药物浓度的升高,Bcl-2表达降低,细胞凋亡率提高,进入深度凋亡期(P<0.05)。荧光显微镜观察与流式细胞术的方法验证了细胞凋亡的情况。本研究进一步阐明了高三尖杉酯碱联合全反式维甲酸诱导早幼粒细胞凋亡过程中,Bcl-2及细胞凋亡与增殖的相关基因表达水平的变化与分子机制,为深入探索药物联合诱导凋亡提供可靠支持,为临床治疗做出基础理论的补充。
The exploration of the mechanism of apoptosis is very important for the treatment of acute promyelocytic leukemia. The B-cell lymphoma-2(Bcl-2) gene family is key to regulate apoptosis. The dynamic balance of positive and negative apoptosis regulatory factors determine the fate of cells. In this study, the expression level of apoptosis-related genes and the trend of cell growth were analyzed. The results showed that the combination of homoharringtonine and all-trans retinoic acid could promote promyelocytic apoptosis more effectively(P<0.05). With the change of drug concentration, the expression of Bcl-2 and related genes increased at first and then decreased. When treated with low concentration of drugs, the expression of anti-apoptotic protein Bcl-2 was increased, and apoptosis was prevented. With the increase of drug concentration, the expression of Bcl-2 decreased, the apoptosis rate increased, and the cells entered the late apoptotic stage. Apoptosis was verified by fluorescence microscopy observation and flow cytometry. This study further clarified the changes and molecular mechanism of Bcl-2 in apoptosis and proliferation-related genes in the process of apoptosis induced by homoharringtonine combined with all-trans retinoic acid, which provided a reliable basis for further exploration of drug-induced apoptosis and made a basic theoretical supplement for clinical treatment.
作者
肖亦舒
梁俊杰
许兰
刘春亚
李冬娜
任立成
XIAO Yi-Shu;LIANG Jun-Jie;XU Lan;LIU Chun-Ya;LI Dong-Na;REN Li-Cheng(Department of Biology,Hainan Medical University,Haikou 571199,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2022年第12期1671-1680,共10页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家自然科学基金(No.31660318,31260269)
海南省自然科学基金高层次人才项目(No.820RC638)资助。