Cytokine-induced killer cells induce apoptosis and inhibit the Akt/nuclear factor-κB signaling pathway in cisplatin-resistant human glioma U87MG cells

Despite advances in the development of treatment methods, glioma remains among the cancer types with a high rate of mortality. Therefore, significant efforts are made to develop novel strategies for the treatment of glioma. Ineffective, long-term cancer chemotherapy can lead to multidrug resistance (MDR), which is one of the most common reasons for the failure of chemotherapy. The present study investigated the effects of cytokine-induced killer cells (CIK) on reversing MDR in cisplatin-resistant U87MG cells (U87MG/DDP). 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 the treatment of U87MG/DDP. An MTS assay, flow cytometric analysis of apoptosis, ELISA, western blotting and reverse transcription quantitative polymerase chain reaction were used to investigate the MDR-reversing effects of CIK as well as the underlying mechanisms. The results showed that cisplatin sensitivity and the apoptotic rate following cisplatin treatment were increased, P-glycoprotein expression was decreased and the intracellular rhodamine-123 content was increased in U87MG/DDP co-cultured with CIK. In addition, the present study also identified increased mRNA and protein expression levels of MDR gene 1 (MDR1), MDR-associated protein 1 (MRP1), B-cell lymphoma 2, Survivin and glutathione S-transferase-pi, while the phosphorylation of AKT and the transcriptional activity of nuclear factor-kappa B in CIK co-cultured U87MG/DDP was decreased. These results indicated that pre-treatment with CIK reversed the MDR of U87MG/DDP, and that CIK-induced apoptosis of U87MG/DDP was associated with the inhibition of Akt/NF-kappa B. These findings suggested that treatment with CIK may be an effective method to enhance the sensitivity of patients with glioma to chemotherapy.