Statin and rottlerin small-molecule inhibitors restrict colon cancer progression and metastasis via MACC1
Fig 8
The effect of rottlerin on metastasis in the mice.
Severe combined immunodeficiency (SCID)-beige mice were intrasplenically transplanted with HCT116-CMVp-Luc cells and treated orally with 100 mg/kg rottlerin daily. Bioluminescence was measured by an intraperitoneal application of 150 mg/kg D-Luciferin and a sequence exposure of 20 s. (A) Acute toxicity was assessed in healthy animals treated with 100 mg/kg rottlerin. Body weight was measured daily for 10 d and is shown relative to day 0. (B, C) The lateral (B) and ventral signals (C) from tumors and metastases were monitored via imaging and quantified over time in solvent- and rottlerin-treated mice. (D, F) Representative pictures showing in vivo and ex vivo imaging of mice and isolated organs from each group on day 24. All images are overlaid with the corresponding bright field pictures. Quantification of the lateral (p < 0.001) (E) and ventral (p < 0.05) (G) signals was performed on day 24. All quantifications are performed using ImageJ software. (H) Human satellite DNA was quantified using quantitative polymerase chain reaction (qPCR) with equivalent amounts of genomic DNA obtained from the liver of each mouse (p < 0.001). (I) MACC1 mRNA levels were determined from the livers using quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) and normalized to human G6PD (p < 0.05). Data represent mean ± SE (n = 9 animals/group), *p < 0.05, ***p < 0.001.