Fig. 7

Larotrectinib promotes the sensitivity of prostate cancer cells to ferroptosis by inhibiting the phosphorylation of TrkA. a Western blot analysis of AGPS protein expression in DU145 and 22Rv1 cells with or without ML210 (10 μM for 8 h) and Larotrectinib (20 nM, overnight) treatment. b The sensitive of ferroptosis in DU145 and 22Rv1 cells with or without ML210 and Larotrectinib treatment. ** P < 0.01, *** P < 0.001. c, d PMP70 staining in DU145 and 22Rv1 cells with or without ML210 and Larotrectinib treatment. ** P < 0.01, *** P < 0.001, **** P < 0.0001. e, f Pca cells were observed by TEM with or without ML210 and Larotrectinib treatment. ** P < 0.01, *** P < 0.001, **** P < 0.0001. g MDA level after treatment with ML210 and/or Larotrectinib in DU145 and 22Rv1 cells. * P < 0.05, ** P < 0.01. h CCK8 essay with the OD values in 6-wells plate after treatment with ML210 and/or Larotrectinib in DU145 and 22Rv1 cells. ** P < 0.01, *** P < 0.001, **** P < 0.0001. i Colony formation assay displayed the DU145 and 22Rv1 cell colony numbers after treatment with ML210 and/or Larotrectinib. j Organoid culture treated with ML210 and/or Larotrectinib from Pca patient tissues. k PCa cells were injected subcutaneously into the right flank of mice after treatment with ML210(50 mg/kg) and/or Larotrectinib (300 mg/kg) every other 24 h. Xenograft growth was measured every other day for 28 days. Tumors in each group at day 28 were harvested and photographed. l Tumor weight in different groups. Data represented as mean ± SD (n = 5). **P < 0.01, **** P < 0.0001. m Tumor volume at each time point. Data represented as mean ± SD (n = 5). n.s., no significance; *P < 0.01, **P < 0.01, ***P < 0.001, **** P < 0.0001