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首页> 外文期刊>Journal of biochemical and molecular toxicology >Sodium valproate sensitizes non-small lung cancer A549 cells to γδ T-cell-mediated killing through upregulating the expression of MICA
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Sodium valproate sensitizes non-small lung cancer A549 cells to γδ T-cell-mediated killing through upregulating the expression of MICA

机译：戊酸钠通过上调云母的表达使非小肺癌A549细胞敏感到γδT细胞介导的杀伤

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摘要

Major histocompatibility complex (MHC) class I chain-related protein A (MICA) is involved in γδ T-cell recognition of target tumor cells. The aim of this study was to investigate the feasibility of utilization of sodium valproate (VPA), a histone deacetylase inhibitor, to sensitize non-small cell lung cancer A549 cells to γδ T-cell-mediated killing. VPA induced a dose-dependent increase in the mRNA and protein expression of MICA in A549 cells. γδ T cells showed cytotoxicity to A549 cells, which was increased by about 50% in the presence of VPA. The concomitant addition of MICA antibody significantly attenuated the VPA-mediated sensitization to γδ T-cell killing. VPA enhanced the cleavage of caspase-3 and caspase-9 in A549 cells cocultured with γδ T cells, and such enhancement was reversed by the MICA antibody. In conclusion, VPA sensitizes tumor cells to γδ T-cell-mediated cytotoxicity through the upregulation of MICA and may thus have benefits in improving γδ T-cell-based cancer immunotherapy.
机译：主要的组织相容性复合物（MHC）I类链相关蛋白A（云母）参与靶肿瘤细胞的γδT细胞识别。本研究的目的是研究利用戊酸钠（VPA），组蛋白脱乙酰酶抑制剂，使非小细胞肺癌A549细胞敏感到γδT细胞介导的杀灭的可行性。 VPA在A549细胞中诱导云母mRNA和蛋白表达的剂量依赖性增加。 γδT细胞显示出A549细胞的细胞毒性，在VPA存在下增加约50％。伴随云母抗体的添加显着减弱了VPA介导的敏化对γδT细胞杀伤。 VPA增强了通过用γδT细胞的A549细胞中的Caspase-3和Caspase-9的切割，并且通过云母抗体反转这种增强。总之，VPA通过云母上调使肿瘤细胞敏感到γδT细胞介导的细胞毒性，因此可以在改善基于γδT细胞的癌症免疫疗法方面具有益处。

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