Sodium Valproate Sensitizes Non-Small Lung Cancer A549 Cells to γδ T-Cell-Mediated Killing through Upregulating the Expression of MICA


  • Contract Grant Sponsor: National Natural Science Foundation of China.

  • Contract Grant Number: 30872261.


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 DOI 10.1002/jbt.21513