Yang Lili, Du Chunjuan, Wu Lei, Yu Jinpu, An Xiumei, Yu Wenwen, Cao Shui, Li Hui, Ren Xiubao
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
National Clinical Research Center for Cancer, Tianjin, China.
J Cancer. 2017 Sep 16;8(16):3287-3295. doi: 10.7150/jca.19426. eCollection 2017.
Cytokine-induced killer (CIK) cells can potentially enhance the tumor-killing activity of chemotherapy. This study aimed to evaluate the effects of CIK cells on cisplatin (DDP) resistance in the human lung adenocarcinoma cell line A549/DDP. The detect resistance index, drug resistance related-genes and cytokine secretion of A549/DDP co-cultured with CIK cells were assayed . 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 (<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 (<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. 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.
细胞因子诱导的杀伤(CIK)细胞可能会增强化疗的肿瘤杀伤活性。本研究旨在评估CIK细胞对人肺腺癌细胞系A549/DDP顺铂(DDP)耐药性的影响。检测了与CIK细胞共培养的A549/DDP的耐药指数、耐药相关基因和细胞因子分泌情况。A549/DDP与CIK细胞共培养后,A549/DDP的DDP耐药性以时间依赖性方式显著降低。与单独培养的A549/DDP细胞相比,与CIK细胞共培养20小时的A549/DDP的DDP耐药性降低了4.93倍(<0.05)。与CIK细胞共培养后,A549/DDP中谷胱甘肽-S-转移酶(GST)-π基因的mRNA和蛋白表达水平显著降低(<0.05)。干扰素(IFN)-γ的分泌随着A549/DDP与CIK细胞共培养时间的延长而显著增加。通过添加中和性IFN-γ可恢复GST-π的表达。CIK细胞可通过降低GST-π表达以增加DDP的蓄积,从而以时间依赖性方式逆转A549/DDP的耐药性。CIK细胞使肺癌细胞对化疗药物重新敏感的作用部分依赖于IFN-γ的分泌。