| Receptor subtype-dependent effects of propofol on metalloproteinase activity, NKG2D ligand expression, and NK cell-mediated cytotoxicity in breast cancer: an in vitro study |
Hyun-Su Ri1, Hyeon Jeong Lee2,3, Jaeho Bae4,5, Ah-Reum Cho2,3, Jae Rin Kim3, Seungbin Park3, Kah Young Lee6, Soeun Jeon6 
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1Department of Anesthesia and Pain Medicine, Kyungpook National University, School of Medicine, Daegu, Republic of Korea
2Department of Anesthesia and Pain Medicine, Pusan National University, School of Medicine, Busan, Republic of Korea
3Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
4Department of Biochemistry, Pusan National University, School of Medicine, Yangsan, Republic of Korea
5PNU BK21 Plus Biomedical Science Education Center, Pusan National University, School of Medicine, Yangsan, Republic of Korea
6Department of Anesthesia and Pain Medicine, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea |
Corresponding author:
Soeun Jeon, Tel: 82-53-600-7707, Fax: 82-53-600-7111,
Email: jseanes@knu.ac.kr
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Received: 7 January 2025 • Revised: 10 March 2025 • Accepted: 31 March 2025 |
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| 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 [ER]- and progesterone receptor [PR]-positive), MDA-MB-453 (human epidermal growth factor receptor 2 [HER2]-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. |
| Key Words:
Breast neoplasms; Intravenous anesthetics; Matrix metalloproteinases; Natural killer cells; NKG2D ligands; Propofol; Triple-negative breast neoplasms |
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