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Updated: Jul 27, 2025

Non-invasive Assessment of the Efficacy of New Therapeutics for Intestinal Pathologies Using Serial Endoscopic Imaging of Live Mice
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NSAID-Au(I) Complexes Induce ROS-Driven DAMPs and Interpose Inflammation to Stimulate the Immune Response against

Zhongren Xu1, Qiuyue Lu1, Min Shan1

  • 1Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, P. R. China.

Journal of Medicinal Chemistry
|June 9, 2023
PubMed

Insights

A novel gold(I) complex, Npx-Au, shows potent antitumor activity against ovarian cancer by inducing oxidative stress and immune responses. This compound offers a promising strategy for combining chemotherapy with immunotherapy.

Area of Science:

  • Medicinal Chemistry
  • Oncology
  • Immunology

Background:

  • Inflammation is implicated in ovarian cancer development.
  • Chemoresistance presents a significant challenge in treating ovarian cancer.

Purpose of the Study:

  • To design and synthesize novel gold(I) complexes derived from NSAIDs or analogues for ovarian cancer treatment.
  • To evaluate the antitumor activity and underlying mechanisms of the most promising gold(I) complex, Npx-Au.

Main Methods:

  • Synthesis of gold(I) complexes.
  • In vitro assessment of antitumor activity and oxidative stress induction.
  • Mechanistic studies involving TrxR activity, COX-2, and PD-L1 expression.
  • In vivo evaluation of immune response stimulation, including DC maturation and T cell infiltration.

Main Results:

  • Gold(I) complex B3 (Npx-Au) exhibited superior antitumor activity compared to cisplatin.
  • Npx-Au induced oxidative stress and damage-associated molecular patterns (DAMPs) by inhibiting thioredoxin reductase (TrxR) activity.
  • Npx-Au treatment led to simultaneous downregulation of cyclooxygenase-2 (COX-2) and programmed death-ligand 1 (PD-L1).
  • In vivo studies showed Npx-Au stimulated immune response by reducing PD-L1, promoting dendritic cell (DC) maturation, and increasing CD4+ and CD8+ T cell infiltration.

Conclusions:

  • The gold(I) complex Npx-Au effectively elicits immunogenic cell death (ICD).
  • Npx-Au demonstrates potential as a therapeutic agent for ovarian cancer by combining chemotherapy and immunotherapy.
  • This study presents a promising strategy for overcoming chemoresistance and enhancing treatment efficacy in ovarian cancer.

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