Fig. 5

GPX4 knockdown synergizes with carboplatin treatment to reduce TNBC burden. (A) Percent survival of metM-Wnt^lung shGPX4 and shScramble cells treated with 5µM ferrostatin-1 or a DMSO control combined with carboplatin for 24 h, relative to the shScramble DMSO-treated control treated with carboplatin (n = 3–4/group). (B, C) Heat map of metM-Wnt^lung shGPX4 (B) and shScramble (C) growth inhibition as determined by BLISS synergy finder utilizing the data from 5 A. (D) Study design to assess the potential of GPX4 expression and chemotherapy treatment to ameliorate metM-Wnt^lung tumor growth in a murine model of TNBC and DIO. Body weights over time (E) and endpoint tumor weights (F) of DIO and control mice receiving orthotopic injection of metM-Wnt^lung shScramble or shGPX4 cells, combined with either carboplatin or vehicle treatment (n = 14–15/group). For the interaction of carboplatin and body weight phenotype, p = 0.0002. For the interaction of carboplatin and GPX4 expression, p = 0.049. Statistical significance determined by two-way ANOVA with Tukey’s multiple comparison test (A, E), or three-way ANOVA with Tukey’s multiple comparison test (F) (*p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001)