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

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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 cytokineinduced 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, Pglycoprotein expression was decreased and the intracellular rhodamine123 content was increased in U87MG/DDP cocultured with CIK. In addition, the present study also identified increased mRNA and protein expression levels of MDR gene 1 (MDR1), MDRassociated protein 1 (MRP1), B-cell lymphoma 2, Survivin and glutathione S-transferaseπ, while the phosphorylation of AKT and the transcriptional activity of nuclear factorκB in CIK cocultured U87MG/DDP was decreased. These results indicated that pretreatment with CIK reversed the MDR of U87MG/DDP, and that CIKinduced apoptosis of U87MG/DDP was associated with the inhibition of Akt/NFκB. These findings suggested that treatment with CIK may be an effective method to enhance the sensitivity of patients with glioma to chemotherapy.
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Document Type: Research Article

Affiliations: 1: Department of Clinical Laboratory, Tianjin Huanhu Hospital, Tianjin 300060, P.R. China 2: Department of Neurosurgery, The Sixth People's Hospital of Chongqing City, Chongqing 400060, P.R. China 3: Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, P.R. China

Publication date: January 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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