地西他滨联合三氧化二砷抑制急性髓系白血病细胞系增殖和促进凋亡

doi:10.16352/j.issn.1001-6325.2023.04.0608

基础医学与临床 ›› 2023, Vol. 43 ›› Issue (4): 608-614.doi: 10.16352/j.issn.1001-6325.2023.04.0608

地西他滨联合三氧化二砷抑制急性髓系白血病细胞系增殖和促进凋亡

刘月, 曹阳, 顾伟英, 商丽梅, 刘琰^*

常州市第一人民医院苏州大学附属第三医院血液科,江苏常州 213003

收稿日期:2022-06-07 修回日期:2022-11-13 出版日期:2023-04-05 发布日期:2023-04-03
通讯作者: ^*liuyan197303@163.com
基金资助:
常州市科技计划(CJ20200118,CJ20210075,CJ20220096);常州市卫生健康青苗人才培养计划(CZQM2020023);江苏省卫生健康委医学科研重点项目(ZD2021043)

Decitabine combined with arsenic trioxide inhibits proliferation and promotes apoptosis of acute myeloid leukemia cell lines

LIU Yue, CAO Yang, GU Weiying, SHANG Limei, LIU Yan^*

Department of Hematology, the First People's Hospital of Changzhou; the Third Affiliated Hospital of Soochow University, Changzhou 213003, China

Received:2022-06-07 Revised:2022-11-13 Online:2023-04-05 Published:2023-04-03
Contact: ^*liuyan197303@163.com

摘要/Abstract

摘要： 目的探讨地西他滨(DAC)联合三氧化二砷(ATO)对急性髓系白血病(AML)细胞增殖、凋亡的影响及潜在分子机制。方法 DAC和ATO单药或联合处理AML细胞系,CCK8法检测细胞活力;Compusyn软件分析两药联合的协同效应;流式细胞术分析细胞凋亡率及细胞周期分布;Western blot检测凋亡相关蛋白多聚ADP核糖聚合酶(PARP)和磷脂酰肌醇3激酶(PI3K)/蛋白激酶B(Akt)蛋白表达。结果 DAC及ATO单药以浓度依赖的方式抑制AML细胞增殖,两药联合可协同抑制AML细胞增殖、诱导细胞凋亡和周期阻滞(P＜0.05)。两药联合显著降低AML细胞PI3K及Akt的磷酸化水平(P＜0.05)。结论 DAC联合ATO可能通过抑制PI3K/Akt通路发挥抗AML效应,为两药联合临床治疗AML提供一定理论依据。

关键词: 地西他滨, 三氧化二砷, 急性髓系白血病, 增殖, 凋亡

Abstract: Objective To investigate the effects of decitabine (DAC) combined with arsenic trioxide (ATO) on proliferation and apoptosis of AML cells and its underlying molecular mechanism. Methods AML cell lines were treated with DAC and ATO alone or in combination. CCK8 was used to detect cell viability;Compusyn software was used to analyze the synergistic effects of the combination treatment;Flow cytometry was applied to determine the apoptosis and cell cycle distribution;Western blot was applied to detect the expressions of poly (ADP-ribose) polymerase (PARP), c-PARP, phosphatidylinositol 3-kinase (PI3K), p-PI3K, protein kinase B (Akt) and p-Akt. Results DAC and ATO alone inhibited AML cell proliferation in a concentration-dependent manner. The combination of the two drugs significantly inhibited cell proliferation, induced apoptosis and cycle arrest of AML cells (P＜0.05). Combination therapy reduced the phosphorylation level of PI3K and Akt (P＜0.05). Conclusions DAC combined with ATO may have anti-AML effect by inhibiting PI3K/Akt pathway, which provides new theoretical basis of DAC+ATO strategy for AML.

Key words: decitabine, arsenic trioxide, acute myeloid leukemia, proliferation, apoptosis

中图分类号:

R733.71

刘月, 曹阳, 顾伟英, 商丽梅, 刘琰. 地西他滨联合三氧化二砷抑制急性髓系白血病细胞系增殖和促进凋亡[J]. 基础医学与临床, 2023, 43(4): 608-614.

LIU Yue, CAO Yang, GU Weiying, SHANG Limei, LIU Yan. Decitabine combined with arsenic trioxide inhibits proliferation and promotes apoptosis of acute myeloid leukemia cell lines[J]. Basic & Clinical Medicine, 2023, 43(4): 608-614.

参考文献

[1]高秋英, 荀利如, 李岚, 等. 上调miR-125a-5p抑制急性髓系白血病细胞系的增殖和侵袭[J]. 基础医学与临床, 2021, 41: 1594-1605.
[2]Appelbaum Fr,Gundacker H,Head Dr,et al. Age and acute myeloid leukemia [J]. Blood,2006,107:3481-3485.
[3]Juliusson G,Antunovic P,Derolf A,et al. Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry [J]. Blood,2009,113:4179-4187.
[4]Keiffer G, Palmisiano N. Acute myeloid leukemia: update on upfront therapy in elderly patients [J]. Curr Oncol Rep,2019,21:71.doi:10.1007/S11912-019-0823-1.
[5]Ossenkoppele G and Löwenberg B. How I treat the older patient with acute myeloid leukemia [J]. Blood,2015,125:767-774.
[6]Gupta S,Yel L,Kim D,et al. Arsenic trioxide induces apoptosis in peripheral blood T lymphocyte subsets by inducing oxidative stress: a role of Bcl-2 [J]. Mol Cancer Ther,2003,2:711-719.
[7]Joe Y,Jeong Jh,Yang S,et al. ATR,PML,and CHK2 play a role in arsenic trioxide-induced apoptosis [J]. J Biol Chem,2006,281:28764-28771.
[8]Christman JK. 5-Azacytidine and 5-aza-2′-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapy [J]. Oncogene,2002,21:5483-5495.
[9]Cashen Af,Schiller Gj,O'donnell Mr,et al. Multicenter,phase II study of decitabine for the first-line treatment of older patients with acute myeloid leukemia [J]. J Clin Oncol,2010,28:556-561.
[10]刘应彬,朱熙君. 地西他滨联合三氧化二砷方案治疗老年中高危骨髓增生异常综合征的应用价值 [J]. 安徽医学,2020,41:943-946.
[11]张彦平,刘蒙蒙,展新荣. 地西他滨联合三氧化二砷治疗老年急性髓系白血病的疗效及安全性 [J]. 新乡医学院学报,2019,36:1163-1166.
[12]陈思思,赵彦平,吴文忠,等. 地西他滨联合三氧化二砷对急性髓系白血病MV4-11细胞增殖和凋亡的影响 [J]. 中国实验血液学杂志,2016,24:1343-1347.
[13]Tamburini J,Elie C,Bardet V,et al. Constitutive phosphoinositide 3-kinase/Akt activation represents a favorable prognostic factor in de novo acute myelogenous leukemia patients [J]. Blood,2007, 110:1025-1028.

[1]	张梦瑶, 牛姝, 蔡静, 赵志刚, 周艳. miR-140-5p靶向HMGB1/IκB-α轴对糖尿病大鼠视网膜病变的影响[J]. 基础医学与临床, 2023, 43(4): 615-620.
[2]	金涛, 杨青山, 吴树金, 朱晓燕, 史宇悰, 牛建雄, 刘林. 内质网应激在骨关节炎中作用的研究进展[J]. 基础医学与临床, 2023, 43(3): 476-480.
[3]	汪博, 张明焕. CIRC_0044235靶向miR-574-5p减轻IL-1β诱导的人软骨细胞损伤[J]. 基础医学与临床, 2023, 43(3): 419-426.
[4]	庞兰, 李佩璠, 郑蕾, 王艺明. 利培酮通过影响Wnt/β-catenin信号通路诱导人成骨细胞系hFob1.19凋亡[J]. 基础医学与临床, 2023, 43(3): 374-379.
[5]	张梦瑶, 牛姝, 蔡静, 张立香, 赵志刚. 丹参酮ⅡA减轻高糖诱导的小鼠足细胞系PMC-5凋亡和氧化应激反应[J]. 基础医学与临床, 2023, 43(2): 277-282.
[6]	王卉, 苏宪, 张赢赢, 褚战亚, 孙朝晖, 张金玲, 张倩倩. 异鼠李素减轻糖尿病视网膜病变大鼠视网膜细胞凋亡[J]. 基础医学与临床, 2023, 43(2): 265-270.
[7]	刘婷婷, 韩超, 赵小玲, 孔为民. 二甲双胍抑制人宫颈鳞癌细胞系SiHa和CaSKi增殖及促进细胞凋亡[J]. 基础医学与临床, 2023, 43(2): 283-288.
[8]	王芳芳, 曹慧媛, 汪婧, 王宁, 黄国良. 上调miR-200c-5p的表达抑制人结直肠癌细胞系SW480增殖[J]. 基础医学与临床, 2023, 43(2): 241-245.
[9]	付士祥, 席月, 丁龙坤, 闫曼, 赵俊, 焦玉东, 吴亮. 鲍曼不动杆菌外膜囊泡诱发人单核-巨噬细胞THP-1的炎性反应[J]. 基础医学与临床, 2023, 43(1): 110-115.
[10]	杨良权, 于淼, 姜茜, 张明慧, 杨海松. miR-504调控蛋白酶体激活因子抑制人乳腺癌细胞系MCF-7增殖及迁移[J]. 基础医学与临床, 2023, 43(1): 95-101.
[11]	顾炜, 祝剑平, 吴品雯. 丙泊酚减轻低氧诱导的大鼠肾上腺嗜铬细胞瘤细胞系PC12炎性反应和细胞凋亡[J]. 基础医学与临床, 2023, 43(1): 137-143.
[12]	董军立, 蔡少康, 严蕾, 蔡毅. 二甲双胍抑制腰椎间盘退变模型兔椎间盘组织的细胞凋亡[J]. 基础医学与临床, 2023, 43(1): 116-122.
[13]	贺晶, 李艳, 王延峰, 鲍慧. FABP4表达上调促进人子宫内膜癌细胞系HEC-1-A增殖和迁移[J]. 基础医学与临床, 2022, 42(9): 1356-1361.
[14]	张晓雷, 刘静, 李朝萍. Circ_0032821参与索拉非尼抑制乳腺癌细胞系T47D增殖、迁移和侵袭[J]. 基础医学与临床, 2022, 42(9): 1350-1354.
[15]	王娟, 张晓燕, 朱爱华, 于宏波, 范新丹, 汤春辉, 姚秀芳. Ku70高表达促进人卵巢癌细胞系的增值并与卵巢癌患者不良预后相关[J]. 基础医学与临床, 2022, 42(9): 1391-1399.

地西他滨联合三氧化二砷抑制急性髓系白血病细胞系增殖和促进凋亡

Decitabine combined with arsenic trioxide inhibits proliferation and promotes apoptosis of acute myeloid leukemia cell lines

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价