Figure 4.

MBZ exerts the strongest anticancer effect among the benzimidazole derivatives on 4T1 and RT-R-4T1 tumor allografts in athymic nude mice. (a–d) For the safety test, the mice were divided into five groups (six mice/group) and treated with ALB, FLU, FBZ, or MBZ (10 mg/kg/mL) by oral gavage daily for 2 consecutive weeks on a schedule of 5-days-on and 2-days-off. After 2 weeks, the mice were sacrificed and plasma alanine aminotransferase (ALT) (a), aspartate aminotransferase (AST) (b), and creatinine levels (c) were measured. Body weights (d) were measured three times a week for 4 weeks. The data represent the mean ± SD (* p < 0.05). (e–n) 4T1 cells or RT-R-4T1 cells (5 × 10⁴ cells/100 μL) were injected subcutaneously, and when tumor volumes reached 100 mm³ (2 weeks after tumor injection), mice were divided into 10 groups (n = 7/each group): (1) 4T1 group, (2) 4T1 group + ALB, (3) 4T1 group + FLU, (4) 4T1 group + FBZ, (5) 4T1 group + MBZ, (6) RT-R-4T1 group, (7) RT-R-4T1 group + ALB, (8) RT-R-4T1 group + FLU, (9) RT-R-4T1 group + FBZ, (10) RT-R-4T1 group + MBZ for 2 consecutive weeks on a schedule of 5-days-on and 2-days-off. Body weights (e,j) and tumor volumes (f,k) were measured three times a week from 7 days after tumor cell injection. The mice were sacrificed on the 28th day after injection, and tumor volumes and (g,h,l,m) lung metastasis (i,n) were measured. The data represent the mean ± SD (* p < 0.05; ** p < 0.01).