Kaempferol Triggers Ferroptosis of Gastric Cancer Cells by the P53/SLC7A11/GPX4 Pathway Based on PCR Array and In Vitro Experiments.

Objective: This work seeks to elucidate the molecular mechanism by which kaempferol inhibits the growth of gastric cancer (GC) cells via the ferroptosis pathway. Methods: The CCK8 detection was used to assess the viability of GC cells treated with kaempferol and oxaliplatin, both individually and in combination, to evaluate potential synergistic effects, while the EDU experiment was employed to determine the impact of kaempferol on DNA synthesis. The PCR array of cell death pathways was used to screen ferroptosis related genes in GC cells intervened by kaempferol and the levels of key markers were quantified with specific assay kits. Mitochondrial morphological alterations were also discovered using the transmission electron microscope. The protein expression levels of NQO1, p53, SLC7A11 and GPX4 in GC cells were analyzed by Western blot experiment following kaempferol treatment. Results: Kaempferol concentration dependently reduced the viability and DNA synthesis of GC cells, with IC50 values of 92.75 μM in HGC27 and 69.74 μM in MKN45 cells. When combined with oxaliplatin, with a Loewe synergy score of 17.621 for HGC27 cells and 13.931 for MKN45 cells, showing a synergistic effect. The PCR array detection indicated that following kaempferol intervention, P53 expression was increased, while NQO1, SLC7A11 and GPX4 expressions were downregulated. Meanwhile, kaempferol markedly decreased GSH levels while elevating MDA, Fe2+ and ROS levels in GC cells. The results of the Western blot experiments corroborated the PCR array findings, demonstrating that kaempferol induced ferroptosis in GC cells by modulating the P53/SLC7A11/GPX4 pathway. Conclusion: Kaempferol could promote ferroptosis in GC cells through the P53/SLC7A11/GPX4 signaling pathway, even for act as a sensitizer agent when combing with oxaliplatin for the treatment of GC.