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.
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.