Oleic Acid and Oleoylethanolamide Decrease Interferon-γ-induced Expression of PD-L1 and Induce Apoptosis in Human Lung Carcinoma Cells

Inhibition of programmed death-ligand 1 (PD-L1) in cancer cells provides a reasonable avenue to prevent cancer progression. Although oleate is known to exert anti-cancer effects, its PD-L1 inhibitory effects have not been proven. This study investigated the effects of oleic acid and an oleic acid metabolite, oleoylethanolamide (OEA), on PD-L1 expression and biomarkers of tumorigenesis in several cancer cell lines, namely A549, HuH-7, MCF-7, DLD-1, and LoVo cells. Specifically, we analyzed the expression of PD-L1 and several apoptosis-related genes using RT-PCR. Interferon-gamma (IFN-γ)-induced modulation of PD-L1 protein expression was investigated using western blotting. Results indicate that IFN-γ stimulation increased the expression of PD-L1 in the chosen cancer cell lines. The IFN-γ-induced expression of PD-L1 was greater in A549 cells, than in other cancerous cell lines. In A549 cells, oleic acid and OEA decreased IFN-γ-induced expression of PD-L1, Bax, Bcl-2, and caspase 3. Oleic acid and OEA decreased IFN-γ-induced phosphorylation of STAT. These results indicate that oleic acid and OEA inhibit PD-1 expression, and induce apoptosis via STAT phosphorylation. Therefore, oleic acid and OEA may prevent cancer formation through STAT phosphorylation with IFN-γ. These findings provide novel insights into the anti-cancer effects of oleic acid-rich oil, such as olive oil.