Fig. 6: AX-53802 and FAK/Src inhibitor cotreatment promotes cell death. | Communications Biology

Fig. 6: AX-53802 and FAK/Src inhibitor cotreatment promotes cell death.

From: Protein covariation networks for elucidating ferroptosis inducer mechanisms and potential synergistic drug targets

Fig. 6

A Western blot showing reduced FAK phosphorylation and Nrf2 protein levels upon FAK/Src inhibitor treatment. STAT3 also exhibited decreased phosphorylation, albeit not statistically significant for the Src inhibitor PP2. No change in ACSL4 protein levels was observed. Data: means ± SEMs (n  =  3). *P < 0.05; **P < 0.01; ***P  <  0.001; ns: not significant (Tukey’s test). B Real-time PCR analysis of NRF2, HMOX1, SLC7A11, GCLM, and ACSL4 in cells treated with FAK/Src inhibitors for 3 h. Transcription of NRF2 and its downstream transcriptional control target genes, HMOX1 and SLC7A11, was significantly reduced by FAK/Src inhibitor treatment. GCLM showed a decreasing trend. Data: means ± SEMs (n  =  3). *P < 0.05; **P < 0.01; ***P  <  0.001; ns not significant (Dunnett’s test). C Schematic representation of the proposed pathway facilitating ferroptosis through FAK/Src inhibitor action. D Viability of cancer cell lines SW480, HT29, HCT116, and HeLa cotreated with AX-53802 and FAK/Src inhibitors for 24 h, measured via the CellTiter-Glo assay. FAK/Src inhibitors induced increased cell death in SW480 and HeLa cells. Cotreatment with PF-228 enhanced cell death in HT29 and HCT116 cells. Fer1 rescued cell death in HT29 cells, with incomplete rescue observed in other cells. Data: means ± SEMs (n  =  3). *P < 0.05; **P < 0.01; ***P  <  0.001; ns not significant (Tukey’s test).

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