The effect of mitochondria inhibition on natural killer cells cytotoxicity in triple-negative breast cancer cells.

Triple-Negative Breast Cancer (TNBC), the most common invasive breast cancer, depicts cancer poor response to conventional therapies. The clinical management of TNBC is a challenging issue. Natural killer (NK) cell therapy in the field of cancer treatment is rapidly growing however, regarding the immunogenicity of breast cancer cells, this type of therapy has shown limited efficacy. Recently, targeting tumor biomarkers has revolutionized the field of cancer therapy. Mitochondria affects apoptosis and innate immunity. Therefore, in this study, mitochondria were inhibited with Tigecycline in stimulating the cytotoxicity of NK cells against TNBC cell lines. MDA-MB-468 and MDA-MB-231 were cultured and treated with IC (the half-maximal inhibitory concentration) level of Tigecycline for 48 h and afterward co-cultured with peripheral blood NK cells for 5 h. Lastly, the inhibitory effects of mitochondria on the cytotoxicity of NK cells and apoptosis of TNBC cells were evaluated. Moreover, the expression of apoptotic-related genes was studied. The results showed that mitochondria inhibition increased NK cells cytotoxicity against TNBC cells. Moreover, NK cell/mitochondria inhibition in a combinative form improved apoptosis in TNBC cells by the upregulation of Bad and Bid expression. In conclusion, Tigecycline inhibited mitochondria and sensitized TNBC cells to NK cell therapy. Therefore, mitochondria inhibition could help NK cells function properly.