The Effect of Sevoflurane on Metalloproteinase and Natural Killer Group2, Member D (NKG2D) Ligand Expression, and Natural Killer Cell-mediated Cytotoxicity in Breast Cancer: An In vitro Study

We investigated the impacts of sevoflurane exposure on matrix metalloproteinase (MMP) expression, natural killer group 2, member D (NKG2D) ligands (UL16-binding proteins [ULBP] 1-3, and major histocompatibility complex class I chain-related molecules [MIC] A/B) expression and ablation, and natural killer (NK) cell-mediated cytotoxicity in breast cancer cells.Three human breast cancer cell lines (MCF-7, MDA-MB-453, and HCC-70) were incubated with 0 (control), 600 (S6), or 1200 μM (S12) sevoflurane for 4 h. The gene expression of NKG2D ligands and their protein expression on cancer cell surfaces were measured using multiplex polymerase chain reaction (PCR) and flow cytometry, respectively. Protein expression of MMP-1 and 2 and concentration of soluble NKG2D ligands were analysed by western blot and enzyme-linked immunosorbent assays, respectively.Sevoflurane downregulated the mRNA and protein expression of the NKG2D ligand in a dose-dependent manner in MCF-7, MDA-MB-453, and HCC-70 cells. However, it did not affect the expression of MMP-1 and 2 or the concentration of soluble NKG2D ligands in MCF-7, MDA-MB-453, and HCC-70 cells. Sevoflurane attenuated NK cell-mediated cancer cell lysis in a dose-dependent manner in MCF-7, MDA-MB-453, and HCC-70 cells (P = 0.040, 0.040, and 0.040, respectively).Our results demonstrated that sevoflurane exposure could attenuate the NK cell-mediated cytotoxicity of breast cancer cells in a dose-dependent manner. This could be attributed to a sevoflurane-induced decrease in the transcription of NKG2D ligands rather than sevoflurane-induced changes in MMP expression and their proteolytic activity.