Telomerase Inhibition Enhances NK Cells-InducedApoptosis in Acute Myeloid Leukemia Cells

Objective: The need to develop new therapies in the treatmentof malignancies has considered the utilize of immune cells especiallynatural killer (NK) cells as a suitable approach. Despitethe valuable anti-tumor effects, using only NK cells haslimited effects. In this s tudy, we aimed to determine the effectof BIBR۱۵۳۲, an human Telomerase Reverse Transcriptase(hTERT) inhibitor, in promoting the cytotoxicity function ofNK cells agains t acute myeloid leukemia (AML) cells.Materials and Methods: AML cell line Kg-۱a were culturedand treated with IC۵۰ value of BIBR۱۵۳۲ for ۴۸ h and subsequentlywith NK cells and its effects on cytotoxicity, cell proliferationand apoptosis were analyzed using AnnexinV /۷AAD,Ki-۶۷ assay, flow cytometry and real-time polymerase chainreaction (PCR) tes ts.Results: Telomerase inhibition (TI) with IC۵۰ value (۵۷.۶۴μM) sensitizes AML cells and increased anti-proliferative effectof NK cells. Besides, TI augmented cytotoxic effect (IFN-γ andCD۱۰۷-a) of NK cells agains t AML cells and significantly increasedinduction of apoptosis. Moreover, BIBR۱۵۳۲ and NKcells synergis tically upregulated expression levels of Bax andBad and Bax/Bcl-۲ ratio and downregulated mRNA expression levels of Bcl-۲, and Bcl-۲/Bax ratio.Conclusion: The combination of BIBR۱۵۳۲ and NK cells synergistically promoted its anti-proliferative effect and inductionof apoptosis through targeting apoptosis related genes such asBax and Bcl-۲.

کلیدواژه ها:

Acute Myeloid Leukemia (AML) ، Apoptosis ، NaturalKiller Cell ، Telomerase