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W1131 is a potent STAT3 inhibitor, triggering ferroptosis. W1131 suppresses cancer progression in gastric cancer cell subcutaneous xenograft model, organoids model, and PDX model. W1131 effectively alleviates chemical resistance of cancer cells to 5-FU . W1131 regulates cell cycle, DNA damage response, and oxidative phosphorylation, including IL6-JAK-STAT3 pathway and ferroptosis pathway.
In Vitro
W1131 (0-2 μM; 72 h) inhibits cell survival, migration, and invasion in gastric cancer AGS cell, and also inhibits colony formation for 3 days treatment. W1131 (0.1-3 μM; 24 h) potently inhibits the phosphorylation of STAT3 in AGS cells. W1131 (1 μM; 48 h) triggers ferroptosis and suppresses GPX4, SLC7A11, and FTH1 expression in gastric cancer. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: AGS cells Concentration: 0.1 μM, 0.3 μM, 1 μM, and 3 μM Incubation Time: 24 hours Result: Dose-dependently decreased the phosphorylated Y705-STAT3, but not STAT5, JAK2, and AKT. ImmunofluorescenceCell Line: AGS cells Concentration: 0.3 μM, 1 μM Incubation Time: 12 hours Result: Significantly promoted lipid ROS formation, and induced Fe 2+ accumulation.
In Vivo
W1131 (3 mg/kg, 10 mg/kg; i.p.; once daily for 2 weeks) inhibits tumor growth dose-dependently, and induces ferroptosis in MGC803 subcutaneous xenograft model in BALB/c-nu/nu mice . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: MGC803 subcutaneous xenografts in mouse Dosage: 3 mg/kg, 10 mg/kg Administration: Intraperitoneal injection; once daily for 2 weeks Result: Inhibited GPX4, SLC7A11, and FTH1 expression level, indicating the induction of ferroptosis. Caused insignificant change of body weight.