ArticleNan fang yi ke da xue xue bao = Journal of Southern Medical University2023
[ARL67156, a small-molecule CD39 inhibitor, enhances natural killer cell cytotoxicity against gastric cancer cells
Article in Nan fang yi ke da xue xue bao = Journal of Southern Medical University, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed, 0 citations in OpenAlex.
- [cGAS-STING agonist cGAMP enhances natural killer cell-mediated cytotoxicity against gastric cancer cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo investigate the effect of ARL67156, a small-molecule inhibitor of CD39, on cytotoxicity of natural killer (NK) cells against gastric cancer cells.
methodsHuman peripheral blood-derived primary NK cells isolated and purified using a magnetic bead antibody method were treated with 100 μmol/L ARL67156 for 24 h, and the signaling pathway of NK cell activation was detected by Western blotting. The level of interferon-γ (IFN-γ) in the supernatant of NK cells co-cultured with gastric cancer cells was detected using ELISA, and NK cell CD107a degranulation was measured with flow cytometry. The cytotoxicity of NK cells against co-cultured gastric cancer cells was evaluated using flow cytometry. In a nude mouse model bearing subcutaneous gastric cancer xenografts, the therapeutic effect of intravenous transfusion of NK cells and intraperitoneal injection of ARL67156 was assessed by measuring the changes in tumor volume.
results(25.97 ± 5.69) % of peripheral blood NK cells from healthy individuals positive for CD39 expression. Treatment with ARL67156 significantly upregulated the activation molecules including NKG2D, DAP10, CD57, and CD16 and reduced the expressions of the inhibitory receptors TIGIT and KIR, thereby promoting the secretion of IFN-γ and CD107a degranulation in NK cells (
conclusionARL67156 activates NK cells through the vav1-Syk signaling pathway to enhance their cytotoxicity against gastric cancer cells, which may serve as a new strategy for NK cell immunotherapy for gastric cancer.
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