Figure 5.

LDHA inhibitor FX11 suppresses ATM-deficient CRPC cell growth. (A) IC₅₀ values of FX11 were measured on C4–2/Ctrl and C4–2/ATM-KO cells treated with a series concentration of FX11 for 72 hours. (B) Lactate production of C4–2/Ctrl and C4–2/ATM-KO cells treated with either DMSO or FX11 for 72 hours. Results are normalized to DMSO group and set as “1”. (C) Intracellular ROS production was detected with DCFDA fluorescence and monitored by flow cytometry at 72 hours post-treatment with either DMSO or 3 μM FX11. Left, median fluorescent intensity. Right, the representative image of histograms of ROS (n = 3 independent experiments). (D) Cell viability of C4–2/Ctrl and C4–2/ATM-KO cells treated with either DMSO or FX11 was determined by MTS assay at the indicated time points (n = 3 replicates). (E & F) Tumor growth of C4–2/Ctrl and C4–2/ATM-KO xenografts treated intraperitoneally with either DMSO or FX11 when tumor reached ~200mm³. Tumor volumes were measured every four days. Top, Representative tumor images in each group. Bottom, The growth curve of xenograft tumors after treatment of vehicle (DMSO) or FX11. All data are depicted as mean ± s.d. * p < 0.05 and ** p < 0.01 by two-tailed Student’s t-test.