Valproic acid enhances myeloma cell sensitivity to natural killer cell-mediated lysis and its mechanism / 白血病·淋巴瘤

ABSTRACT

Objective To investigate the effect of valproic acid (VPA) on NKG2D-ligand expression in ARK,OPM2 human myeloma cell lines and their sensitization to natural killer (NK) cell-mediated Killing.Methods Different concentrations of VPA from 0-5.0 mmol/L were used to treat ARK,OPM2 cells respectively,then the cell viabilities were tested by flow cytometry (FCM).Real-time quantitative-PCR and FCM were used to detect the changes in mRNA,protein levels of NKG2D-ligand respectively in the two cell lines treated with 1 mmol/L VPA for 48 hours.The calcein-release-assay (CARE-LASS) was carried out to detect cytotoxic changes of NK cells against mydoma cells after VPA treatment.Results VPA induced the expression of MICA/B,ULBP2 (P ＜ 0.05) and in turn enhanced the NK cytotoxicity on myeloma cells.The enhancing effect of VPA was blocked by NK cells pretreated with anti-NKG2D mAb (P ＜ 0.05).The primary mechanism of NK cell killing of myeloma cells was perforin/granzyme-mediated.Conclusion VPA can induce the expression of MICA/B,ULBP2 in ARK,OPM2 cells,thereby enhancing the cytotoxicity against myeloma cells,which implies a new mechanism of anticancer approach and may be a new approach in myeloma immunotherapy.