Valproic acid sensitizes pancreatic cancer cells to natural killer cell-mediated lysis by upregulating MICA and MICB via the PI3K/Akt signaling pathway.
In: BMC Cancer, Jg. 14 (2014), Heft 1, S. 370
Online
academicJournal
Zugriff:
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. [ABSTRACT FROM AUTHOR]
Titel: |
Valproic acid sensitizes pancreatic cancer cells to natural killer cell-mediated lysis by upregulating MICA and MICB via the PI3K/Akt signaling pathway.
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Autor/in / Beteiligte Person: | Shi, Pengfei ; Yin, Tao ; Zhou, Feng ; Cui, Pengfei ; Gou, Shanmiao ; Wang, Chunyou |
Link: | |
Zeitschrift: | BMC Cancer, Jg. 14 (2014), Heft 1, S. 370 |
Veröffentlichung: | 2014 |
Medientyp: | academicJournal |
ISSN: | 1471-2407 (print) |
DOI: | 10.1186/1471-2407-14-370 |
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