NOD2 silencing promotes cell apoptosis and inhibits drug resistance in chronic lymphocytic leukemia by inhibiting the NF‐κB signaling pathway

Abstract

AbstractRecent years have witnessed increasing studies on the effect of epigenetic silencing of genes in the progression of chronic lymphocytic leukemia (CLL). This study investigates whether the nucleotide binding oligomerization domain containing 2 (NOD2) participates in the cell apoptosis and drug resistance of CLL cells. Cells were treated with adriamycin (ADR), etoposide, aclacinomycin and daunorubicin. After treatment, drug resistance and cell proliferation were examined to detect the inhibitory effect of ADR on cell proliferation; flow cytometry to identify ADR accumulation, the cell cycle distribution and apoptosis after transfection, and rhodamine 123 accumulation and efflux tests to assess P‐glycoprotein (P‐gp) function. NOD2 silencing or inhibition of the nuclear factor kappa‐B (NF‐κB) signaling pathway suppressed the multidrug resistance level in CLL, the inhibition rate, and cell proliferation caused by ADR at concentrations of approximately 0.25−1.5 μmol/L. Greater accumulation of ADR was observed in the CLL‐AAT cell line than in the CLL‐AAT/A02 cell line, but NOD2 silencing or inhibition of the NF‐κB signaling pathway further increased the accumulation of ADR drugs in the CLL‐AAT cell line and inhibited the drug efflux pump function of P‐gp. Additionally, NOD2 silencing or NF‐κB signaling pathway inhibition increased the apoptotic rate. The results of this study indicate that NOD2 promotes cell apoptosis and reduces the drug resistance of CLL by inhibiting the NF‐κB signaling pathway.