A prospective study on the inhibition of gastric cancer by 164.88° recombinant humanized type III collagen through remodeling of extracellular matrix.

Safe and effective strategies for gastric cancer are urgently needed. Previous studies showed that reduced type III collagen is associated with tumor growth and metastasis. This study found that 164.88°recombinant humanized type III Collagen (rhCol III) at 5 mg/mL and 10 mg/mL significantly inhibited the proliferation, migration, and invasion of gastric cancer cells, without affecting normal gastric mucosal epithelial cells. RNA sequencing analysis revealed that rhCol III inhibits gastric cancer by remodeling the tumor extracellular matrix, inhibiting the PI3K-Akt signaling pathway, and inducing ferroptosis. Anti-ITGB4 antibody partially reversed rhCol III-induced inhibition of gastric cancer cells and downstream PI3K-Akt/ferroptosis responses. In vivo experiments in nude mice confirmed its anti-tumor efficacy. When MKN45 cells were injected with 10 mg/mL rhCol III or PBS, the tumor weight in the rhCol III group decreased to 55.53% of the control group after 23 days. When MKN45 cells were inoculated for 1 week, followed by injection of rhCol III at different concentrations or PBS, the tumor weight in the groups treated with 10 mg/mL, 20 mg/mL, and 30 mg/mL rhCol III decreased to 46.15%, 56.21%, and 32.38% of the control group, respectively, after 19 days. This study explores the inhibitory effects of rhCol III on gastric adenocarcinoma and its mechanisms, providing a theoretical basis for new therapeutic strategies for gastric cancer.