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

Cytokine-Induced Killer Cells Modulates Resistance to Cisplatin in the A549/DDP Cell Line.
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细胞因子诱导的杀伤细胞调节 A549/DDP 细胞系对顺铂的耐药性

DOI:
10.7150/jca.19426
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发表时间:
2017
期刊:
影响因子:
3.9
通讯作者:
Ren X
Ren X
中科院分区:
医学3区
文献类型:
--
作者:
Yang L;Du C;Wu L;Yu J;An X;Yu W;Cao S;Li H;Ren X

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研究背景细胞因子诱导的杀伤细胞(CIK)能增强化疗的肿瘤杀伤活性。目的探讨CIK细胞对人肺腺癌细胞系A549/DDP顺铂耐药的影响。方法体外检测A549/DDP与CIK细胞共培养后的耐药指数、耐药相关基因及细胞因子分泌情况。结果A549/DDP与CIK细胞共培养后,A549/DDP对DDP的耐药性明显降低,并呈时间依赖性。CIK细胞与A549/DDP共培养20 h后,A549/DDP细胞对DDP的耐药性较单独培养时下降4.93倍(P<0.05)。与CIK细胞共培养后,A549/DDP细胞GST-π基因的mRNA和蛋白表达水平均显著降低(P<0.05)。随着A549/DDP与CIK细胞共培养时间的延长,IFN- γ的分泌量沿着增加。加入中和性IFN-γ后,GST-π的表达恢复。结论CIK细胞可通过降低GST-π的表达,增加DDP的蓄积,逆转A549/DDP的耐药性,并呈时间依赖性。CIK细胞对肺癌细胞化疗药物的增敏作用部分依赖于IFN-γ的分泌。
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. ResultsAfter 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. ConclusionCIK 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.
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影响因子: 2.6
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