ArticleInternational journal of molecular sciences2026
DNAM-1-Stimulated NK-92 Cells Exert Preferential Cytotoxic and Apoptosis-Associated Effects on Hormone-Independent Solid Tumor Cell Lines.
Article in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Anti-CD226 antibody-mediated stimulation of NK-92 cells (sNK-92) represents a potential immunotherapeutic approach; however, its cytotoxic and apoptosis-associated effects in hormone-independent solid tumors remain insufficiently characterized. This study investigated the activity of sNK-92 cells against PC3 castration-resistant prostate cancer and SH-SY5Y neuroblastoma cell lines, using PNT1A normal prostate epithelial and BJ normal dermal fibroblast cells as non-malignant controls. Cytotoxicity was assessed by CCK-8 assay at target-to-effector (T:E) ratios of 1:1, 1:5, and 1:10, and markers historically associated with the intrinsic (BAX, caspase-9), extrinsic (caspase-8), and executioner (caspase-3) apoptotic pathways were evaluated quantitatively by ImageJ-based corrected total cell fluorescence (CTCF) analysis. sNK-92 cells produced significant ratio-dependent cytotoxicity against PC3 and SH-SY5Y cells, reaching 23.76% and 26.29%, respectively, at the 1:10 T:E ratio, with sNK-92 producing significantly greater cytotoxicity than unstimulated NK-92 at this ratio in both cell lines and additionally at the 1:5 ratio in SH-SY5Y cells; no significant reduction in CCK-8 viability was detected in PNT1A or BJ cells at any ratio. Quantitative immunofluorescence analysis demonstrated substantially increased relative fluorescence intensity of all four apoptosis-associated markers in sNK-92-treated PC3 and SH-SY5Y cells compared with their corresponding controls and, in most comparisons, with NK-92-treated cells, whereas changes observed in the PNT1A and BJ non-malignant models examined were markedly smaller. These findings provide preliminary quantitative evidence that anti-CD226-stimulated NK-92 cells exert a preferential cytotoxic effect on the tumor cell models examined, relative to the non-malignant models tested, and induce changes in apoptosis-associated markers consistent with engagement of apoptotic signaling. Further orthogonal validation is warranted.
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