Effect of CIK on multidrug-resistance reversal and increasing the sensitivity of ADR in K562/ADR cells

Oncol Lett. 2014 Oct;8(4):1778-1782. doi: 10.3892/ol.2014.2337. Epub 2014 Jul 10.

Abstract

Leukemia is a leading cause of cancer-related mortality in children worldwide, and multidrug-resistance (MDR) is a main reason for tumor chemotherapy failure. The present study investigated the effects of ADR following incubation with cytokine-induced killer (CIK) cells on reversing MDR in K562/ADR cells. Mononuclear cells were isolated from the peripheral blood of healthy individuals and cultured in vitro in the presence of a combination of cytokines to generate CIK for K562/ADR cell treatment. A decreased level of P-glycoprotein expression and glutathione (GSH), an increased intracellular Rh-123 content, decreased mRNA and protein expression levels of MDR gene 1, MDR-associated protein 1, GSH S-transferase-π, B-cell lymphoma 2 and Survivin, and the decreased phosphorylation of AKT and the transcriptional activity of nuclear factor-κB and activator protein 1 were detected following ADR treatment in CIK co-cultured K562/ADR cells. Additionally, the level of ADR sensitivity and the apoptosis rate were increased in the CIK co-cultured K562/ADR cells. These results indicate that pre-treatment with CIK could reverse the MDR of K562/ADR cells, and that patients would be most likely to benefit from the combination of chemotherapy and CIK therapy.

Keywords: Adriamycin; K562/ADR cells; cytokine-induced killer; multidrug-resistance.