Fig. 6: Statins and niclosamide synergize in suppression of CRC cell wound healing and metastasis.

HCT116 human colorectal cancer cells with endogenous MACC1 and S100A4 expression were treated with three concentrations (1.25, 2.5 and 5 µM) of atorvastatin and niclosamide (0.25, 0.5 and 1 µM) alone and in combinations thereof (A). After drug application in vitro wound healing was monitored for 48 h using the IncuCyte live cell imaging system. Atorvastatin and niclosamide were able to reduce wound closure compared to control cells. Combining a statin with niclosamide increased this effect synergistically. Results are shown as means ± SEM of at least 3 experiments. Treating xenografted SCID beige mice (n = 60, 10 animals per group) with human equivalent doses of either atorvastatin (3.25 mg/kg, 20 mg per patient per day), fluvastatin (3.25 mg/kg, 20 mg per patient per day) or niclosamide (250 mg/day, 1.5 g per patient per day) alone reduced metastasis formation in the liver. Confirming the in vitro results, the combination of the tested drugs, each statin with niclosamide, was superior to single drug treatment (B, D). While visualization of xenografted cells by luminescence did not show significant reductions just before mouse killing (C), human cell load in the murine liver was quantifiably reduced in human satellite DNA specific qPCR (D). Numeric results are shown as mean ± SEM, and level of significance indicated as per ANOVA and Dunnett’s correction for multiple testing.