Format

Send to

Choose Destination
BMC Cancer. 2014 May 25;14:370. doi: 10.1186/1471-2407-14-370.

Valproic acid sensitizes pancreatic cancer cells to natural killer cell-mediated lysis by upregulating MICA and MICB via the PI3K/Akt signaling pathway.

Author information

1
Pancreatic Disease Institute, Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei Province 430022, P, R, China. gousm@163.com.

Abstract

BACKGROUND:

Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is reported to exert anti-tumor effects by upregulating the expression of the natural killer group 2D (NKG2D) ligands on tumor cells; however, the mechanisms vary in different tumor types, and the effect and mechanism of action of VPA in pancreatic cancer cells are unknown.

METHODS:

The present study evaluated the effect of VPA to susceptibility of pancreatic cancer cells to the NK cell-mediated lysis in vitro and in vivo. Then we investigated the mechanism which the effect of VPA depend on.

RESULTS:

The lactate dehydrogenase assay (LDH) and xenograft experiment demonstrated that VPA significantly sensitized pancreatic cancer cells to NK cell-mediated lysis in vitro and in vivo. Quantitative real time- polymerase chain reaction (qRT-PCR) and flow cytometry demonstrated that VPA upregulated the mRNA and cell surface expression of the NKG2D ligands major histocompatibility complex class I-related chain A and B (MICA and MICB) in pancreatic cancer cells. Effects of VPA both in vitro and in vivo were significantly attenuated by the PI3K/Akt pathway inhibitor LY294002 or a siRNA targeting PI3K catalytic subunit alpha isoform (PI3KCA).

CONCLUSION:

VPA enhances the susceptibility of pancreatic cancer cells to NK cell-mediated cytotoxicity both in vitro and in vivo by upregulating the expression of MICA and MICB via a PI3K/Akt signaling pathway-dependent mechanism.

PMID:
24885711
PMCID:
PMC4076062
DOI:
10.1186/1471-2407-14-370
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center