N-acetyl cysteine induces quiescent-like pancreatic stellate cells from an active state and attenuates cancer-stroma interactions

Abstract Background Pancreatic stellate cells (PSCs) occupy the majority of pancreatic cancer microenvironment, contributing to aggressive behavior (PCCs). Recently, anti-fibrotic agents have proven be an effective strategy against cancer, but clinical trials shown little efficacy, and driving mechanism remains unknown. N-acetyl-cysteine (NAC) is often used for pulmonary cystic fibrosis. Pioglitazone, agonist peroxisome proliferator-activated receptor gamma, was habitually type II diabetes, recently reported inhibit metastasis PCCs. However, few studies focused on effects these two cancer-stromal interactions. Method We evaluated expression ?-smooth muscle actin (?-SMA) number lipid droplets in PSCs cultured with or without NAC. also changes invasiveness, viability, oxidative level PCCs after NAC treatment. Using indirect co-culture system, we investigated migration Combined treatment Pioglitazone were In vivo, co-transplanted KPC-derived organoids evaluate Pioglitazone’s combination therapy subcutaneous tumor formation splenic xenografted mouse models. Results vitro, inhibited at a low concentration, not those significantly reduced stress ?-SMA, collagen I PSCs, which apparently present quiescent-like state high droplets. Co-cultured mutually promoted each other. promotion attenuated by maintained NAC-induced reactivated PCC-supernatant, enhanced chemosensitivity suppressed growth liver fewer stromal components level. Conclusion activated induces that this pioglitazone