Fig. 7. Schematic diagram of the proposed mechanism by which thiostrepton modulates ferroptosis via the STAT3/GPX4 signalling pathway.

In general, in pancreatic cancer cells, TST does not regulate the function of SLC711A but instead alters the expression of STAT3. Activated STAT3 binds to the GPX4 promoter region to promote its transcription. Therefore, GPX4 downregulation by TST subsequently promotes the production of lipid ROS, leading to lipid peroxidation that ultimately induces ferroptosis.