NSAID-Au(I) Complexes Induce ROS-Driven DAMPs and Interpose Inflammation to Stimulate the Immune Response against Ovarian Cancer.

Abstract

Inflammation contributes to the development of ovarian cancer, and chemoresistance is a principal obstacle in ovarian cancer treatment. Herein, we designed and synthesized a series of gold(I) complexes derived from NSAIDs or their analogues. Among them, complex B3 (Npx-Au) displayed higher antitumor activity than cisplatin and other gold(I) complexes. Npx-Au could induce oxidative stress and the damage-associated molecular patterns (DAMPs) process by the inhibition of TrxR activity. Mechanistic studies revealed that simultaneous downregulation of COX-2 and PD-L1 was observed after Npx-Au treatment. Interestingly, in vivo experiments demonstrated that Npx-Au treatment could stimulate the immune response via reducing the expression of PD-L1, inducing DC maturation and increasing the infiltration of T (CD4+ and CD8+) cells. Collectively, our studies found that the gold(I) complex Npx-Au could elicit immunogenic cell death (ICD) and provide a promising strategy for chemotherapy combined with immunotherapy in the treatment of ovarian cancer.