Fig. 6.

Combination of lorlatinib with GPX4 inhibition causes melanoma repression in vivo.

(A) Treatment schedule of tumor-bearing mice for drug administration. Nude mice were injected with sgCtrl or sgGPX4 (2 × 10⁶) and treated with lorlatinib (10 mg/kg orally, every day) and vehicle at day 6 when the tumor size reached 50–100 mm [3]. Lip-1 was given 10 mg/kg intraperitoneally every day. Tumor volume was calculated every three days. (B-E) Tumor weight (B), percentage of change in tumor volume (C), tumor volume (D), and body weight (E) in the indicated groups. (F) IHC staining with antibodies against 4-HNE and GPX4 in the indicated group. Magnification, 400 × . Scale bar = 50 μm. (G) Quantification by Image J of 4-HNE in IHC staining. (H) Gene expression of IGF1R, SREBF1 and SCD within normal skin and melanoma patients in Xiangya cohorts. Num (N) = 77, num (T) = 99. N, normal skin; T, tumor. (I) Pearson correlation assay between IGF1R, SREBF1 and SCD gene expression in Xiangya melanoma cohorts. (J) Kaplan-Meier survival analysis with log-rank test of GPX4 and IGF1R gene expression in Xiangya melanoma cohorts. Num (high GPX4 & high IGF1R) = 15, Num (high GPX4 & low IGF1R) = 14, Num (low GPX4 & high IGF1R) = 14, Num (low GPX4 & low IGF1R) = 16. (K) Schematic summary for the findings in the present study. One-way ANOVA analysis was performed in B, C, D, G, J. Two-tailed unpaired Student's t-test was performed in H. *, P < 0.05; **, P < 0.01; ***, P < 0.001.