THBS1 knockdown and baicalin induce pyroptosis via the NF-κB-NLRP3-Caspase-1 axis in gastric cancer cells

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide.
• Understanding the molecular mechanisms driving GC progression is crucial for developing effective treatments.
• Thrombospondin 1 (THBS1) has been implicated in various cancers, but its specific role in GC requires further elucidation.

Purpose of the Study:

• To investigate the role of THBS1 in gastric cancer.
• To evaluate the synergistic effects of Baicalin and THBS1 knockdown on GC cells.
• To explore the underlying molecular mechanisms, including pyroptosis and cell cycle regulation.

Main Methods:

• Differential gene expression analysis and protein-protein interaction network construction.
• Functional assays (cell behavior, G1 arrest, apoptosis, LDH release, ROS levels) on GC cells.
• Western blot analysis of the NF-κB-NLRP3-Caspase-1 axis and in vivo xenograft models.

Main Results:

• THBS1 is highly expressed in GC cells; its knockdown inhibits cell proliferation and induces apoptosis.
• Combined treatment with Baicalin and THBS1 knockdown synergistically enhances anti-GC effects, promoting pyroptosis and oxidative stress.
• The combination treatment activates the NLRP3 inflammasome and regulates the NF-κB-NLRP3-Caspase-1 axis, significantly inhibiting tumor growth in vivo.

Conclusions:

• THBS1 knockdown combined with Baicalin demonstrates significant synergistic anti-gastric cancer activity.
• This combination therapy inhibits GC progression by modulating cell behavior, cell cycle, and pyroptosis via the NF-κB-NLRP3-Caspase-1 pathway.
• Targeting THBS1 in conjunction with Baicalin presents a promising novel therapeutic strategy for gastric cancer.