ArticleCancer biology & therapy2017
Synergistic effect of cytokine-induced killer cell with valproate inhibits growth of hepatocellular carcinoma cell in a mouse model.
Article in Cancer biology & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Timely meta-analysis on the efficacy of adoptive immunotherapy for hepatocellular carcinoma patients after curative therapy.PloS one · 2017Pooled it
- Cytokine-Induced Killer Cell Immunotherapy Reduces Recurrence in Patients with Early-Stage Hepatocellular Carcinoma.Cancers · 2025Article
- Current and novel approaches in the pharmacological treatment of hepatocellular carcinoma.World journal of gastroenterology · 2023Review
- Hepigenetics: A Review of Epigenetic Modulators and Potential Therapies in Hepatocellular Carcinoma.BioMed research international · 2020Review
- Targeting the crosstalk between cytokine-induced killer cells and myeloid-derived suppressor cells in hepatocellular carcinoma.Journal of hepatology · 2019Article
- Sustained efficacy of adjuvant immunotherapy with cytokine-induced killer cells for hepatocellular carcinoma: an extended 5-year follow-up.Cancer immunology, immunotherapy : CII · 2019Article
- Cytokine-induced killer cells as a feasible adoptive immunotherapy for the treatment of lung cancer.Cell death & disease · 2018Article
- Review
- Immunotherapy for Hepatocellular Carcinoma: Current Advances and Future Expectations.Journal of immunology research · 2018Review
- Evaluation of cell death pathways initiated by antitumor drugs melatonin and valproic acid in bladder cancer cells.FEBS open bio · 2017Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveLong-term prognosis of hepatocellular carcinoma (HCC) remains poor owing to the lack of treatment options for advanced HCC. Cytokine-induced killer (CIK) cells are ex vivo expanded T lymphocytes expressing both NK- and T-cell markers. CIK cell therapy alone is insufficient for treating advanced HCC. Thus, this study aimed to determine whether treatment with CIK cells combined with valproic acid (VPA) could provide a synergistic effect to inhibit tumor growth in a mouse model of HCC.
methodsUpregulation of natural killer group 2D (NKG2D) ligands (retinoic acid early inducible 1 [RAE-1], mouse; major histocompatibility complex class I polypeptide-related sequence A [MIC-A], human) were evaluated by FACS. VPA concentrations that did not reduce tumor volume were calculated to avoid VPA cytotoxicity in a C3H mouse model of HCC. CIK cells were generated from mouse splenocytes using interferon gamma, a CD3 monoclonal antibody, and interleukin 2. The potential synergistic effect of CIK cells combined with VPA was evaluated in the mouse model and tissue pathology was investigated.
resultsAfter 40 h of incubation with VPA, RAE-1 and MIC-A expression were increased in 4 HCC cell lines compared with that in control (2.3-fold in MH-134, 2.4-fold in Huh-7, 3.7-fold in SNU-761, and 6.5-fold in SNU-475). The maximal in vivo VPA dosage that showed no significant cytotoxicity compared with control was 10 mg/kg/day. CIK cells were well generated from C3H mouse splenocytes. After 7 d of treatment with CIK cells plus VPA, a synergistic effect was observed on relative tumor volume in the mouse model of HCC. While the relative tumor volume in untreated control mice increased to 11.25, that in the combination treatment group increased to only 5.20 (P = 0.047).
conclusionsThe VPA-induced increase in NKG2D ligands expression significantly enhanced the effects of CIK cell therapy in a mouse model of HCC.
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