ArticleBMC cancer2014
Valproic acid sensitizes pancreatic cancer cells to natural killer cell-mediated lysis by upregulating MICA and MICB via the PI3K/Akt signaling pathway.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 65 citations in OpenAlex.
- HIF-1α: A Key Factor Mediating Tumor Cells from Digestive System to Evade NK Cell Killing via Activating Metalloproteinases to Hydrolyze MICA/B.Biomolecules · 2025Review
- Targeting the HLA-E-NKG2A axis in combination with MS-275 enhances NK cell-based immunotherapy against DMG.Journal of experimental & clinical cancer research : CR · 2025Article
- Sodium valproate enhances efficacy of NKG2D CAR-T cells against glioblastoma.Frontiers in immunology · 2024Article
- Synergistic integration of histone deacetylase inhibitors apparently enhances the cytokine-induced killer cell efficiency in multiple myeloma via the NKG2D pathway.Clinical & translational immunology · 2024Article
- The Class I HDAC Inhibitor Valproic Acid Strongly Potentiates Gemcitabine Efficacy in Pancreatic Cancer by Immune System Activation.Biomedicines · 2022Article
- Bispecific Antibodies Progression in Malignant Melanoma.Frontiers in pharmacology · 2022Review
- Application of natural killer cells in pancreatic cancer.Oncology letters · 2021Review
- Three-Dimensional Culture Models to Study Innate Anti-Tumor Immune Response: Advantages and Disadvantages.Cancers · 2021Review
- Article
- Natural Killer Cells and Anti-Cancer Therapies: Reciprocal Effects on Immune Function and Therapeutic Response.Cancers · 2021Review
- Regulation of valproic acid induced EMT by AKT/GSK3β/β-catenin signaling pathway in triple negative breast cancer.Molecular biology reports · 2021Article
- Valproic Acid: A Promising Therapeutic Agent in Glioma Treatment.Frontiers in oncology · 2021Review
- Leveraging NKG2D Ligands in Immuno-Oncology.Frontiers in immunology · 2021Review
- The Oncoprotein SKI Acts as A Suppressor of NK Cell-Mediated Immunosurveillance in PDAC.Cancers · 2020Article
- Metformin inhibits cervical cancer cell proliferation by modulating PI3K/Akt-induced major histocompatibility complex class I-related chain A gene expression.Journal of experimental & clinical cancer research : CR · 2020Article
- Entinostat augments NK cell functions via epigenetic upregulation of IFIT1-STING-STAT4 pathway.Oncotarget · 2020Article
- Epithelial-mesenchymal transition may be involved in the immune evasion of circulating gastric tumor cells via downregulation of ULBP1.Cancer medicine · 2020Article
- Refocusing the Use of Psychiatric Drugs for Treatment of Gastrointestinal Cancers.Frontiers in oncology · 2020Review
- Review
- Exploring the Drug Repurposing Versatility of Valproic Acid as a Multifunctional Regulator of Innate and Adaptive Immune Cells.Journal of immunology research · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundValproic 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.
methodsThe 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.
resultsThe 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).
conclusionVPA 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.
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