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

Globally, gastric cancer (GC) continues to be the primary cause of death due to cancer. This study aimed to investigate the role of <i>THBS1</i> in GC and assess the potential synergistic effects of Baicalin and <i>THBS1</i> knockdown on GC cells. Differential expression analysis of GC-related datasets was conducted, and a protein-protein interaction (PPI) network was established. Key targets were screened, and prognostic genes were identified using a Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model. Functional assays assessed the effects of <i>THBS1</i> knockdown and Baicalin treatment on GC cell behavior and pyroptosis. <i>THBS1</i> was highly expressed in GC cells, and its knockdown reduced cell behavior, inducing G1 arrest and apoptosis. Combined with Baicalin, these effects were enhanced, synergistically inhibiting GC cell behavior. Detection kits showed that knockdown of <i>THBS1</i> or baicalin treatment increased lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) levels, while their combination further exacerbated oxidative stress and cell damage. Western blot (WB) analysis revealed that baicalin combined with <i>THBS1</i> knockdown synergistically promoted pyroptosis by activating the NLRP3 inflammasome and regulating the NF-κB-NLRP3-Caspase-1 axis. <i>In vivo</i> xenograft models demonstrated that <i>THBS1</i> knockdown or combined treatment with baicalin significantly inhibited GC progression. These results suggest that <i>THBS1</i> knockdown combined with baicalin can inhibit GC progression by regulating cell behavior, cell cycle, pyroptosis, and the NF-κB-NLRP3-Caspase-1 axis in GC cells. This mechanism is expected to become a new target for GC treatment.