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ABT-199 和双氢青蒿素联合用药对人 U937 和 KG-1 癌细胞生长和凋亡的影响。

The Effects of ABT-199 and Dihydroartemisinin Combination on Cell Growth and Apoptosis in Human U937 and KG-1 Cancer Cells.

机构信息

Department of Molecular Medicine and Biotechnology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran.

Department of Anatomy, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

Asian Pac J Cancer Prev. 2024 Jan 1;25(1):343-350. doi: 10.31557/APJCP.2024.25.1.343.

DOI:10.31557/APJCP.2024.25.1.343
PMID:38285802
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10911724/
Abstract

INTRODUCTION

Change in the balance of Bcl-2 family proteins is one of the main reasons for resistance of tumor cells to ABT-199. In this study, the effect of dihydroartemisinin on cell growth, apoptosis and sensitivity of the AML cells to ABT-199 was investigated.

METHODS

Cell proliferation and survival were assessed by trypan blue staining and MTT assay, respectively. Cell apoptosis was measured by Hoechst 33342 staining and caspase-3 activity assay. The expression levels of Bcl-2, Mcl-1 and Bax mRNA were tested by qRT-PCR.

RESULTS

Our data showed that combination therapy significantly reduced the IC50 value and synergistically decreased the AML cell survival and growth compared with dihydroartemisinin or ABT-199 alone. Treatment with each of ABT-199 or dihydroartemisinin alone clearly enhanced the Bax mRNA expression and inhibited the expression of Mcl-1 and Bcl-2 mRNA. Inhibition of Mcl-1 mRNA by dihydroartemisinin was associated with enhancement of apoptosis induced by ABT-199 in AML cells.

CONCLUSION

In conclusion, dihydroartemisinin not only triggers the intrinsic pathway of apoptosis, but also can increase the sensitivity of the AML cells to ABT-199 via suppression of Mcl-1 expression.

摘要

简介

Bcl-2 家族蛋白平衡的改变是肿瘤细胞对 ABT-199 产生耐药性的主要原因之一。在本研究中，研究了双氢青蒿素对 AML 细胞的生长、凋亡和对 ABT-199 的敏感性的影响。

方法

通过台盼蓝染色和 MTT 测定分别评估细胞增殖和存活。通过 Hoechst 33342 染色和 caspase-3 活性测定测量细胞凋亡。通过 qRT-PCR 测试 Bcl-2、Mcl-1 和 Bax mRNA 的表达水平。

结果

我们的数据表明，与单独使用双氢青蒿素或 ABT-199 相比，联合治疗显著降低了 AML 细胞的 IC50 值，并协同降低了 AML 细胞的存活和生长。单独使用 ABT-199 或双氢青蒿素处理明显增强了 Bax mRNA 的表达，并抑制了 Mcl-1 和 Bcl-2 mRNA 的表达。双氢青蒿素抑制 Mcl-1 mRNA 与 ABT-199 在 AML 细胞中诱导的凋亡增强有关。

结论

总之，双氢青蒿素不仅触发了细胞的内在凋亡途径，而且通过抑制 Mcl-1 表达，还能增加 AML 细胞对 ABT-199 的敏感性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fc3/10911724/495f8d6373ec/APJCP-25-343-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fc3/10911724/e65870140919/APJCP-25-343-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fc3/10911724/ebfdbf17b789/APJCP-25-343-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fc3/10911724/84bb46422425/APJCP-25-343-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fc3/10911724/495f8d6373ec/APJCP-25-343-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fc3/10911724/e65870140919/APJCP-25-343-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fc3/10911724/ebfdbf17b789/APJCP-25-343-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fc3/10911724/84bb46422425/APJCP-25-343-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fc3/10911724/495f8d6373ec/APJCP-25-343-g004.jpg

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