siRNA-mediated Silencing of Survivin Inhibits Proliferation and Enhances Etoposide Chemosensitivity in Acute Myeloid Leukemia Cells

Abstract

Background: Overexpression of survivin, a known inhibitor of apoptosis, is associated with tumor progression and drug resistance in numerous malignancies, including leukemias. The aim of this study was to investigate the effect of a specific survivin small interference RNA (siRNA) on proliferation and the sensitivity of HL-60 acute myeloid leukemia (AML) cells to the chemotherapeutic drug etoposide. Materials and Methods: The cells were transfected with siRNAs using Lipofectamine™2000 transfection reagent. Relative survivin mRNA and protein levels were measured by quantitative real-time PCR and Western blotting, respectively. Trypan blue exclusion assays were performed to monitor tumor cell proliferation after siRNA transfection. The cytotoxic effects of etoposide and survivin siRNA, alone and in combination, on leukemic cells were determined using MTT assay. Apoptosis was assessed by ELISA cell death assay. Results: Survivin siRNA markedly reduced both mRNA and protein expression levels in a time-dependent manner, leading to distinct inhibition of cell proliferation and increased spontaneous apoptosis. Surprisingly, survivin siRNA synergistically increased the cell toxic effects of etoposide. Moreover, survivin down-regulation significantly enhanced its induction of apoptosis. Conclusions: Our study suggests that down-regulation of survivin by siRNA can trigger apoptosis and overcome drug resistance of leukemia cells. Therefore, survivin siRNA may be an effective adjuvant in AML chemotherapy

Elevated Serum Ferritin Levels in Patients with Hematologic Malignancies

“…Hematologic malignancies are a common disease in Asian Pacific areas (Feng et al, 2013;Jiang et al, 2013;Karami et al, 2013;Khodabandehloo et al, 2013;Kooshyar et al, 2013;Li et al, 2013;Liu et al, 2013;Ozbas-Gerceker et al, 2013;Qin et al, 2013;Shan et al, 2013). As our present study confirmed, the level of serum ferritin of patients with hematologic malignancies was significantly increased.…”

Silencing of High Mobility Group Isoform I-C (HMGI-C) Enhances Paclitaxel Chemosensitivity in Breast Adenocarcinoma Cells (MDA-MB-468)

“…In similar study, Karami et al showed specific silencing of survivin expression by siRNA enhanced sensitivity of leukemic cells to etoposide. 29,30 In other studies, they showed MDR1 down-regulation synergistically increased the cytotoxic effects of oxaliplatin and etoposide on oxaliplatin resistant SW480 and etoposide resistant HL-60 cells.…”

MEKK3 and Survivin Expression in Cervical Cancer: Association with Clinicopathological Factors and Prognosis

“…Survivin is the smallest member of the inhibitor of apoptosis protein family with cell periodicity and is expressed only in G2/M phase (Kitamura et al, 2006;Srivastava et al, 2012). Survivin BIR function by binding with mitotic microtubules influences the activity of Caspase-3 of most downstream effector molecule during apoptosis and inhibition of apoptosis (Wand et al, 2004;Karami et al, 2013). Increased expression of survivin is associated with the occurrence and development of cervical cancer and is expected to become a molecular marker for early diagnosis and prognosis in cervical cancer (Lu et al, 2010;Wu et al, 2012).…”