Title:ZEB2 Knock-down Induces Apoptosis in Human Myeloid Leukemia HL-60 Cells
Volume: 21
Issue: 2
关键词:
急性骨髓性白血病,ZEB2(锌指E-Box结合同源异型盒2),RNAi,靶向治疗,细胞凋亡,白血病。
摘要:
Introduction: Acute myeloid leukemia (AML) is the most prevalent type of cancer in
the adult hematopoietic system. Conventional therapies are associated with unfavorable side effects
in individuals diagnosed with AML. These after-effects with partial remission reflect the urgent
need for novel therapeutic approaches for inducing apoptosis, specifically in malignant cells, without
affecting other cells. As a transcription factor (TF), ZEB2 (Zinc Finger E-Box Binding Homeobox
2) regulates the expression of specific genes in normal conditions. However, increased expression
of ZEB2 is reported in various cancers, especially in AML, which is related to a higher degree
of apoptosis inhibition of malignant cells. In this work, the role of ZEB2 in apoptosis inhibition is
surveyed through ZEB2 specific knocking-down in human myeloid leukemia HL-60 cells.
Materials and Methods: Transfection of HL-60 cells was conducted using ZEB2-siRNA at concentrations
of 20, 40, 60, and 80 pmol within 24, 48, and 72 h. After determining the optimum dose
and time, flow cytometry was used to measure the apoptosis rate. The MTT assay was also utilized
to evaluate the cytotoxic impact of transfection on the cells. The expression of candidate genes was
measured before and after transfection using qRT-PCR.
Results: According to obtained results, suppression of ZEB2 expression through siRNA was associated
with the induction of apoptosis, increased pro-apoptotic, and decreased anti-apoptotic gene expression.
Transfection of ZEB2-siRNA was also associated with reduced cell proliferation and viability.
Conclusion: Our study results suggest that ZEB2 suppression in myeloid leukemia cells through
apoptosis induction could be a proper therapeutic method.