Apoptosis induction and migration suppression through regulation of IGF-1R/FoxO signaling pathways in Panc1 pancreatic cancer cells by hAMSCs secretome: An in vitro cell-based therapy

• Pancreatic cancer is recognized lethal cancer with a poor prognosis and no symptoms. • Cell-based therapy (or stem cells) in cancer treatment have become well-established. • Secretome enables to regulate IGF-1R/FoxO signaling pathways in Panc1 cancer cells. Pancreatic cancer often referred to as the “king of cancers,” is a disease with no symptoms and lacks effective therapy. Current treatment options for pancreatic cancer have not been successful, highlighting the need for new therapeutic avenues with minimal side effects and improved effectiveness. In recent years, new cell-based therapies using stem cells or their derivatives have shown promise in treating various diseases, including cancer. Here, we aimed to explore the impact of the secretome of human amniotic mesenchymal stem cells (hAMSCs) on Panc1 pancreatic cancer cells, focusing on the insulin-like growth factor 1 receptor (IGF-1R)/FoxO signaling pathways. To achieve this, we developed a co-culture system utilizing 6-well plates transwell. After 72 hours, cell death and cell invasion in hAMSCs-treated Panc1 cells were assessed using Western blot, Scratch assay, and DAPI staining. Our results showed an increase in the expression levels of AKT, AMPK, FasL, and cleaved caspases 3/9, while there was a decrease in FoxO, IGF-1R, PI3K, 14-3-3, p-FoxO, MMP3, Integrin α3, and Integrin β6 expression. These findings suggest that hAMSCs’ secretome promotes cell death and inhibits cell invasion in Panc1 cells, indicating its potential as a novel targeted therapy approach for pancreatic cancer.