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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| Authors: | Xian‐zhi Du Qiong‐ya Li Fa‐wang Du Zheng‐guang He Juan Wang |
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| Affiliation: | 1. Department of Respiratory Medicine, The Second Affiliated Hospital, Chongqing Medical University, , Chongqing, 400010 People's Republic of China;2. Department of Respiratory Medicine, Suining Central Hospital, , Suining, 629000 People's Republic of China |
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| Abstract: | 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. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:492‐498, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21513 |
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| Keywords: | Apoptosis MICA Non‐Small Lung Cancer Sodium Valproate Immunotherapy |
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