A novel peptide RR-171 derived from human umbilical cord serum induces apoptosis and pyroptosis in pancreatic cancer cells

Human umbilical cord serum is full of molecules that play vital roles in foetal development. This study aimed to explore the effects of RR-171, a novel peptide derived from umbilical cord serum, on pancreatic cancer cells and to elucidate its mechanisms. The anti-pancreatic cancer properties of RR-171 were detected by a cell counting kit-8, colony formation, flow cytometry, LDH release and EdU incorporation assays. RNA sequencing and gene enrichment analysis were applied to identify the differentially expressed genes and enriched pathways. Western blotting analysis was used to detect the expression of proteins. A subcutaneous xenograft model was used to examine the effect of RR-171 on pancreatic cancer cells in vivo. The results demonstrated that RR-171 inhibited the viability, proliferation and colony formation of pancreatic cancer cells in a dose-dependent manner. Gene enrichment analysis revealed that RR-171 inhibits the Wnt signaling pathway. Moreover, RR-171 significantly induced apoptosis and pyroptosis in pancreatic cancer cells in a dose-dependent manner. Z-VAD-FMK partly reversed the proapoptotic effect of RR-171, and VX-765 partly reversed the pro-pyroptotic effect of RR-171. Finally, RR-171 inhibited the growth of pancreatic cancer cells in a subcutaneous xenograft mice model and suppressed the expression of Ki-67 and PCNA in tumors. In conclusion, RR-171 induces apoptosis and pyroptosis through multiple pathways and inhibits pancreatic cancer growth, suggesting that RR-171 might be a potential agent for the treatment of pancreatic cancer.