biostudies-literatureUnknown8(1)Guo HPatients with pancreatic cancer (PC) show dismal prognosis and high mortality. The development of PC is associated with the overactivation of STAT3. Here, we have determined that the non-peptide small molecule Stattic inhibits PC development by targeting STAT3. In vitro, Stattic treatment time- and dose-dependently inhibited proliferation of pancreatic cancer cells (PCCs) by reducing c-Myc expression and enhancing p53 activity. Consequently, p-Rb, cyclin D1, Chk1, and p21 (cell cycle proteins) were downregulated, and PCCs were arrested at the G1 phase, which was also confirmed by decreased Ki67 expression and unaltered PCNA expression. In addition, Stattic-induced mitochondrial-dependent apoptosis by elevating cleaved caspase-3, and Bax, cytochrome C levels, while reducing expression of BcCell death discovery116https://www.ebi.ac.uk/biostudies/studies/S-EPMC8921333biostudies-literatureInhibition of STAT3^Y705 phosphorylation by Stattic suppresses proliferation and induces mitochondrial-dependent apoptosis in pancreatic cancer cells.PMC8921333Yang XWang MChen QChen JGuo HXiao YXie LTong YChen CBai YYuan ZZhang QfalseInhibition of STAT3^Y705 phosphorylation by Stattic suppresses proliferation and induces mitochondrial-dependent apoptosis in pancreatic cancer cells.Patients with pancreatic cancer (PC) show dismal prognosis and high mortality. The development of PC is associated with the overactivation of STAT3. Here, we have determined that the non-peptide small molecule Stattic inhibits PC development by targeting STAT3. In vitro, Stattic treatment time- and dose-dependently inhibited proliferation of pancreatic cancer cells (PCCs) by reducing c-Myc expression and enhancing p53 activity. Consequently, p-Rb, cyclin D1, Chk1, and p21 (cell cycle proteins) were downregulated, and PCCs were arrested at the G1 phase, which was also confirmed by decreased Ki67 expression and unaltered PCNA expression. In addition, Stattic-induced mitochondrial-dependent apoptosis by elevating cleaved caspase-3, and Bax, cytochrome C levels, while reducing expression of Bc2022-01-01T00:00:00Z2022 Mar2025-04-04T12:40:38.227Z2025-04-04T12:40:38.227ZS-EPMC89213333528854110.1038/s41420-022-00922-9