J Cancer 2017; 8(16):3287-3295. doi:10.7150/jca.19426

Research Paper

Cytokine-Induced Killer Cells Modulates Resistance to Cisplatin in the A549/DDP Cell Line

Lili Yang1, 3, 4, 5, 6*, Chunjuan Du1, 3, 4, 5, 6*, Lei Wu1, 3, 4, 5, 6, Jinpu Yu1, 3, 4, 5, 6, Xiumei An1, 3, 4, 5, 6, Wenwen Yu1, 3, 4, 5, 6, Shui Cao2, 3, 4, 5, 6, Hui Li1, 3, 4, 5, 6✉, Xiubao Ren1, 2, 3,4, 5, 6✉

1. Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China;
2. Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China;
3. National Clinical Research Center for Cancer, Tianjin, China;
4. Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China;
5. Key Laboratory of Cancer Prevention and Therapy, Tianjin, China;
6. Tianjin's Clinical Research Center for Cancer, Tianjin, China.
* These authors contributed equally to this article.

Abstract

Background Cytokine-induced killer (CIK) cells can potentially enhance the tumor-killing activity of chemotherapy. Objective This study aimed to evaluate the effects of CIK cells on cisplatin (DDP) resistance in the human lung adenocarcinoma cell line A549/DDP. Methods The detect resistance index, drug resistance related-genes and cytokine secretion of A549/DDP co-cultured with CIK cells were assayed in vitro. Results After A549/DDP co-culture with CIK cells, the DDP resistance of A549/DDP significantly decreased in a time-dependent manner. The DDP resistance of A549/DDP co-cultured with CIK cells for 20 h decreased 4.93-fold compared with that of A549/DDP cells cultured alone (P<0.05). The mRNA and protein expression levels of the glutathione-S-transferase (GST) -π gene in A549/DDP significantly decreased after co-culture with CIK cells (P<0.05). The secretion of interferon (IFN)- γ significantly increased along with the co-culture time of A549/DDP with CIK cells. The expression of GST-π was restored by adding the neutralizing IFN-γ. Conclusion CIK cells can reverse the drug resistance of A549/DDP in a time-dependent manner by reducing GST-π expression to increase the accumulation of DDP. The effect of CIK cells on re-sensitizing lung cancer cells to the chemotherapy drug was partially dependent on the secretion of IFN-γ.

Keywords: cytokine-induced killer cells, chemotherapy resistance, lung cancer, GST-π, IFN-γ.

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How to cite this article:
Yang L, Du C, Wu L, Yu J, An X, Yu W, Cao S, Li H, Ren X. Cytokine-Induced Killer Cells Modulates Resistance to Cisplatin in the A549/DDP Cell Line. J Cancer 2017; 8(16):3287-3295. doi:10.7150/jca.19426. Available from http://www.jcancer.org/v08p3287.htm