Immunology Research Center, Tabriz University of Medical sciences, Tabriz, Iran.
Department of Immunology, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Asian Pac J Cancer Prev. 2022 Jul 1;23(7):2523-2530. doi: 10.31557/APJCP.2022.23.7.2523.
Acute myeloid leukemia (AML) is a type of blood cancer characterized by fast cellular proliferation. Myeloid cell leukemia-1 (Mcl-1) and survivin, as anti-apoptotic proteins, are involved in cancer growth and resistance to chemotherapy. The aim of this study was to examine the combination effect of Mcl-1 and survivin specific siRNAs on chemosensitivity of the human HL-60 AML cells.
SiRNAs transfection was performed by using Lipofectamine™2000 reagent. The mRNA expression was analyzed by real-time quantitative PCR. The apoptosis analysis was measured by ELISA cell death assay.
siRNAs markedly suppressed mRNA expression levels of Mcl-1 and survivin in a time-dependent manner, resulting in reduction of leukemic cell proliferation and enhanced spontaneous cell death. Surprisingly, Mcl-1 siRNA and survivin siRNA synergistically enhanced the cell toxic effects of etoposide. Furthermore, down-regulation of Mcl-1 and survivin significantly enhanced the apoptotic effect of etoposide.
Our investigation suggests that suppression of Mcl-1 and survivin by siRNA can effectually inhibit cell growth and overcome chemoresistance of AML cells. Therefore siRNAs may be an important adjuvant in chemotherapy for AML patients.
急性髓细胞白血病（AML）是一种以细胞快速增殖为特征的血液癌症。髓样细胞白血病-1（Mcl-1）和存活素作为抗凋亡蛋白，参与癌症的生长和对化疗的耐药性。本研究旨在研究 Mcl-1 和存活素特异性 siRNA 的联合作用对人 HL-60 AML 细胞化疗敏感性的影响。
通过 Lipofectamine™2000 试剂进行 siRNA 转染。通过实时定量 PCR 分析 mRNA 表达。通过 ELISA 细胞死亡测定法测量细胞凋亡。
siRNA 显著抑制 Mcl-1 和存活素的 mRNA 表达水平，呈时间依赖性，导致白血病细胞增殖减少和自发细胞死亡增加。令人惊讶的是，Mcl-1 siRNA 和 survivin siRNA 协同增强依托泊苷的细胞毒性作用。此外，下调 Mcl-1 和 survivin 显著增强了依托泊苷的促凋亡作用。
我们的研究表明，siRNA 抑制 Mcl-1 和 survivin 可以有效地抑制细胞生长并克服 AML 细胞的化疗耐药性。因此，siRNA 可能是 AML 患者化疗的重要辅助手段。
