Fascaplysin Induces Apoptosis and Ferroptosis, and Enhances Anti-PD-1 Immunotherapy in Non-Small Cell Lung Cancer...

Area of Science:

• Marine Natural Products
• Cancer Biology
• Immunotherapy

Background:

• Fascaplysin is a sponge-derived natural product with known anticancer properties.
• The precise mechanisms of fascaplysin against non-small cell lung cancer (NSCLC) remain largely unelucidated.
• Understanding its action is crucial for developing novel NSCLC therapeutics.

Purpose of the Study:

• To investigate the anti-NSCLC mechanisms of fascaplysin.
• To explore fascaplysin's effects on cell migration, epithelial-mesenchymal transition (EMT), apoptosis, and ferroptosis.
• To evaluate fascaplysin's potential in combination with anti-PD-1 immunotherapy.

Main Methods:

• Cell migration assays and Western blotting to assess Wnt/β-catenin signaling and EMT markers.
• Analysis of reactive oxygen species (ROS), Fe²⁺ levels, and ferroptosis-associated proteins.
• Assessment of apoptosis induction and PD-L1 expression in NSCLC cells.
• In vivo studies using a syngeneic mouse model to evaluate anti-tumor efficacy with anti-PD-1 therapy.

Main Results:

• Fascaplysin inhibited NSCLC cell migration by regulating the Wnt/β-catenin pathway and reversing EMT.
• The compound induced both apoptosis and ferroptosis in NSCLC cells, evidenced by increased ROS and Fe²⁺, and altered protein expression.
• Fascaplysin treatment upregulated PD-L1 expression in lung cancer cells.
• Combined fascaplysin and anti-PD-1 therapy demonstrated enhanced anti-tumor efficacy in vivo.

Conclusions:

• Fascaplysin exhibits anti-NSCLC effects through the induction of apoptosis and ferroptosis.
• It modulates key signaling pathways and enhances the efficacy of anti-PD-1 immunotherapy.
• Fascaplysin represents a promising therapeutic candidate for NSCLC treatment.