Figure 6.

The combination of fluvastatin and dipyridamole delays prostate tumor growth. (A) Male NOD/SCID mice were injected subcutaneously with 5 million LNCaP cells. Once tumors reached a volume of 200 mm³, the mice were randomized to receive 50 mg/kg/day fluvastatin (oral), 120 mg/kg/day dipyridamole (i.p. injection), the combination or vehicle controls. The drug combination resulted in significantly reduced tumor volumes. Error bars represent the mean ± SD, n = 4–5 mice per treatment group, *p < 0.05 (one-way ANOVA with Tukey's multiple comparisons test). (B) After 12 days of treatment, tumors were excised, fixed and assayed for TUNEL staining by IHC. TUNEL-positive cells were quantified and representative images are shown (scale bar = 100 μm). Box plot with whiskers representing minimum and maximum values, n = 4–5 mice per treatment group, *p < 0.05 (one-way ANOVA with Tukey's multiple comparisons test). (C) Male NOD-SCID mice were engrafted subcutaneously with LTL-484 patient-derived xenograft tissue. Once tumors reached a volume of 200 mm³, the mice were randomized to receive fluvastatin and dipyridamole (as above) or vehicle controls. The drug combination resulted in significantly reduced tumor volumes. Error bars represent the mean ± SD, n = 6–9 mice per treatment group, *p < 0.05 (Student t test, unpaired, two-tailed). (D) After 24 days of treatment, the mice were euthanized, and the tumors were excised and weighed. Tumors from the mice treated with the drug combination weighed significantly less than those from the mice treated with the vehicle controls. Box plot with whiskers representing minimum and maximum values, n = 6–9 mice per treatment group, *p < 0.05 (Student t test, unpaired, two-tailed).