J Cancer 2017; 8(16):3287-3295. doi:10.7150/jca.19426
Cytokine-Induced Killer Cells Modulates Resistance to Cisplatin in the A549/DDP Cell Line
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.
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
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.