MicroRNA-374b inhibits liver cancer progression via down regulating programmed cell death-1 expression on cytokine-induced killer cells

被引:44
作者
Huang, Fen [1 ]
Wang, Bo [2 ]
Zeng, Jiangzheng [1 ]
Sang, Shenggang [3 ]
Lei, Junhua [1 ]
Lu, Yanda [1 ]
机构
[1] Hainan Med Univ, Dept Med Oncol, Affiliated Hosp 1, 31 Longhua Rd, Haikou 570102, Hainan, Peoples R China
[2] Hainan Gen Hosp, Dept Emergency, Haikou 570311, Hainan, Peoples R China
[3] Hainan Med Univ, Affiliated Hosp 1, Dept Clin Lab, Haikou 570102, Hainan, Peoples R China
关键词
liver cancer; microRNA-374b; cytokine-induced killer; programmed cell death-1; ANTI-PD-1; ANTIBODY; PD-1; HEPATITIS; SAFETY; BLOCKADE; MIR-374B; PATHWAY; PROLIFERATION; DYSREGULATION; DYSFUNCTION;
D O I
10.3892/ol.2018.7951
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Programmed cell death-1 (PD-1) is an oncogene associated with suppressing proliferation and cytokine production of T cells in the progression of liver cancer. microRNAs (miRs) regulate gene expression via specific binding to the target 3'untranslated region of mRNA. In the present study, miR-374b was indicated to interact with PD-1 and affect the tumor-targeting capacity of cytokine-induced killer (CIK) cells. miR-374b inhibitor significantly increased PD-1 expression in CIK cells. A synthetic small interfering (si) RNA targeting PD-1 was employed to silence the expression level of PD-1 in CIK cells. Then, the antitumor effect of siPD-1 in CIK cells was investigated. In vitro study demonstrated that IFN-gamma secretion and the concentration of lactate dehydrogenase were significantly increased in the PD-1 knockdown group; however, the viability of HepG2 cells in the PD-1 knockdown group had significantly decreased, compared with the HepG2 cells in the negative control group. In vivo study indicated that mice inoculated with HepG2 cells and CIK cells with PD-1 knocked down had a significantly smaller tumor volume, compared with the control group. To conclude, human CIK cells transfected with siPD-1 can target liver cancer cells and enhance immunotherapy efficacy, and therefore they have potential in the immunotherapy of liver cancer.
引用
收藏
页码:4797 / 4804
页数:8
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