NLG-919 combined with cisplatin to enhance inhibitory effect on cell migration and invasion via IDO1-Kyn-AhR pathway in human nasopharyngeal carcinoma cell.

As a common aggressive head and neck cancer, nasopharyngeal carcinoma (NPC) received cisplatin treatment as a first-line chemotherapy. Platinum-induced resistance is a major limitation of current treatment strategy in the advanced NPC. Increased indoleamine 2,3-dioxygenase (IDO1) activities are found in cisplatin-resistant NPC cells versus cisplatin-sensitive NPC cells. As an IDO1 immunosuppressant, NLG-919 has entered clinical phase I to treat advanced solid tumors. In order to reverse cisplatin resistance, we investigated the combinatory application of cisplatin and NLG-919 in NPC treatment. In vitro biological studies on cisplatin-resistant and cisplatin-sensitive NPC cells were taken to imply that the combination of NLG-919 and cisplatin got a stronger impact on the induction of cell apoptosis and the inhibition of cell migration, exploring superior effect of anti-tumor over single drug. We proved that the mechanism of the combined therapy could inhibit the activity of IDO1, blocking amino acid tryptophan (Trp) conversion to kynurenine (Kyn) through the kynurenine pathway (KP), which further inhibited the aryl hydrocarbon receptor (AhR) expression. Our study underscored the combination of cisplatin and NLG-919 as a potent therapeutic way for reversal of cisplatin resistance.