Work

Receptor subtype-dependent effects of propofol on metalloproteinase activity, NKG2D ligand expression, and NK cell-mediated cytotoxicity in breast cancer: an in vitro study

Year: 2025

Type: article

Abstract: BACKGROUND: The effects of propofol, a commonly used intravenous anesthetic, on the breast cancer tumor microenvironment are not well understood. This study examined the influence of propofol on natural killer group 2, member D (NKG2D) ligand expression, matrix metalloproteinase (MMP)-mediated immune evasion, and natural killer (NK) cell-mediated cytotoxicity in breast cancer cells. METHODS: We studied three human breast cancer cell lines representing distinct receptor subtypes: MCF-7 (estrogen receptor - and progesterone receptor-positive), MDA-MB-453 (human epidermal growth factor receptor 2-positive), and HCC-70 (triple-negative). Cells were treated with propofol at concentrations of 0 μg/ml (control; C), 4 μg/ml (P4), or 8 μg/ml (P8). Assessments included mRNA and protein expression of NKG2D ligands, NK cell cytotoxicity, protein levels of MMP-1 and MMP-2, and concentrations of soluble NKG2D ligands. RESULTS: In MCF-7 and HCC-70 cell lines, propofol upregulated the mRNA and protein expression of NKG2D ligands in a dose-dependent manner, enhancing NK cell-mediated lysis. In contrast, in MDA-MB-453 cell lines, propofol downregulated the mRNA and protein expression of NKG2D ligands, resulting in diminished NK cell-mediated lysis. Across all receptor subtypes, propofol did not affect the expression of MMP-1 or MMP-2 or the concentration of soluble NKG2D ligands. CONCLUSIONS: Our results demonstrate that propofol exerts receptor subtype-dependent effects on NK cell-mediated immunosurveillance in breast cancer cell lines, potentially mediated by changes in the transcription of NKG2D ligands rather than by alterations in MMP expression or their proteolytic activity.

Source: Korean Journal of Anesthesiology

DOI: 10.4097/kja.25011