FIGURE 5.

ALA treatment suppresses tumor growth in vivo. (A) Scheme of in vivo ALA treatment in the NCI-H460 cell xenograft model. Two million NCI-H460 cells were subcutaneously inoculated, and after 5 days, mice were injected with DMSO or ALA (10 and 20 mg/kg in DMSO) intravenously (i.v.) at days 1, 3, 5, 8, 10, 13, 15, and 18. At day 19 of treatment, mice were sacrificed for tumor weight and immunoblotting analysis. (B) ALA inhibited tumor growth in NCI-H460 xenograft models. Average and SD of the tumor volumes (mm³) versus time. NCI-H460 cells were injected subcutaneously into mice (N = 6/group), and then mice were treated with or without ALA (10 and 20 mg/kg) every 2 days for 21 days. Tumor sizes were measured every 2 days. **p < 0.01, ##p < 0.01. vs vehicle. (C) Averages and SDs of nude mouse weights versus the time (mean weight ± SD; n = 6/group). (D) Images of xenograft tumor tissues dissected from each mouse at the end of experiments. (E) Mean weight of tumors were measured. Data were presented as mean ± SD, **p < 0.01, ##p < 0.01. vs vehicle. (F) Expression of AKR1C1 and phosphorylation of STAT3 in the tumor tissues were detected by immunoblot. GAPDH was used as loading control. (G) Schematic overview of the mechanism of ALA in NSCLC cells. ALA directly binds to AKR1C1, decreases the downstream phosphorylation of STAT3, and ultimately, this process leads to the death of the NSCLC cells.