Natural killer cells in combination with the inhibition of telomerase induced apoptosis in Acute Myeloid Leukemia cells

IF 2.3 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Ali Rafat , Khadijeh Dizaji Asl , Zeinab Mazloumi , Mehdi Talebi , Hojjatollah Nozad Charoudeh
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引用次数: 0

Abstract

Background

Recent trends in developing new treatments for cancers, highlight the use of immune cells particularly Natural Killer (NK) cells, as promising therapeutic strategies. While NK cells exhibit significant anti-tumor effects, their effectiveness is often limited. This study investigated the impact of BIBR1532, a human telomerase reverse transcriptase (hTERT) inhibitor, on improving the cytotoxicity of NK cells against Acute Myeloid Leukemia (AML) cells.

Methods

Primary AML cells and Kg-1a cell lines were cultured and treated with the half-maximal inhibitory concentration (IC50) of BIBR1532 for 48 h. The treated cells were then co-cultured with NK cells, after which cytotoxicity, cell proliferation, and apoptosis were assessed using Annexin V/7-AAD and Ki-67 expression analysis. Finally, apoptosis-related genes and proteins, hTERT gene and caspase 3/7 activity were studied.

Results

The Telomerase Inhibition (TI) in primary AML and Kg-1a cells with IC50 values of 38.75 μM and 57.64 μM, respectively, sensitized the AML cells and enhanced the anti-proliferative effects of NK cells. The combination of BIBR1532 and NK cells led to increased apoptosis, as indicated by the upregulation of the Bax and Bad genes, an increased Bax/Bcl-2 ratio, caspase 3/7 activity, Bax protein and a downregulation of mRNA expression levels of Bcl-2, Bcl-xl and decreased Bcl-2 protein.

Conclusion

The findings of this study demonstrate that the concurrent application of BIBR1532 and NK cells promotes apoptosis and reduces proliferation by targeting apoptosis-related genes and proteins such as Bax and Bcl-2.

Abstract Image

自然杀伤细胞联合端粒酶抑制诱导急性髓系白血病细胞凋亡
近年来,在开发新的癌症治疗方法的趋势中,免疫细胞特别是自然杀伤细胞(NK)的使用是一种很有前途的治疗策略。虽然NK细胞具有显著的抗肿瘤作用,但其有效性往往有限。本研究探讨了人类端粒酶逆转录酶(hTERT)抑制剂BIBR1532对提高NK细胞对急性髓性白血病(AML)细胞毒性的影响。方法培养原代AML细胞和Kg-1a细胞系,用BIBR1532的半最大抑制浓度(IC50)处理48h后,与NK细胞共培养,通过Annexin V/7-AAD和Ki-67表达分析评估细胞毒性、细胞增殖和凋亡。最后,研究细胞凋亡相关基因和蛋白、hTERT基因和caspase 3/7活性。结果端粒酶抑制(TI)对原代AML和Kg-1a细胞有增敏作用,其IC50值分别为38.75 μM和57.64 μM,增强了NK细胞的抗增殖作用。BIBR1532与NK细胞结合导致细胞凋亡增加,Bax和Bad基因上调,Bax/Bcl-2比值、caspase 3/7活性、Bax蛋白升高,Bcl-2、Bcl-xl mRNA表达水平下调,Bcl-2蛋白表达水平降低。结论本研究结果表明,BIBR1532与NK细胞同时应用,通过靶向Bax、Bcl-2等凋亡相关基因和蛋白,促进细胞凋亡,降低细胞增殖。
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来源期刊
Biochemistry and Biophysics Reports
Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics
CiteScore
4.60
自引率
0.00%
发文量
191
审稿时长
59 days
期刊介绍: Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.
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