Figure 1.

Inhibitory effects of CP and dabigatran etexilate co-treatment on 4T1 tumor growth, metastases, and thrombin antithrombin (TAT) complex. Balb/c mice were orthotopically injected with 2 × 10⁴ 4T1 cells in the inguinal mammary fat pad. When the primary tumors were between 25–50 mm³ in size, treatment was initiated with i.p. injection of cyclophosphamide (CP) at 50 mg/kg (A, B) or 25 mg/kg (C, D, E) once weekly with or without dabigatran etexilate (Dab) administration by oral gavage (80 mg/kg twice daily, Mon-Fri, and 120 mg/kg once a day on weekends). Mice were sacrificed 24 hrs after last CP treatment. (A, C) Graph shows tumor growth rate and volume in mice bearing 4T1 tumors under different treatments (n = 5–9 mice/treatment group; mean volume per time point ± SEM). (B, D) Lungs were perfused with India ink to visualize surface lung metastatic nodules of mice treated with 50 mg/kg (B) or 25 mg/kg (D) of CP. (E) Platelet poor plasma (PPP) was used to determine levels of TAT by ELISA assay. * = p < 0.05 compared to control vehicle-treated tumor bearing mice.