Figure 1.

Niclosamide inhibits the proliferation of uveal melanoma cells in vitro and in vivo. (A) UM cells (92.1, Mel270, Omm1 and Omm2.3) were exposed to escalating concentrations of niclosamide for 72 h, and the cell viability was determined by MTS assay. (B) UM cells (92.1, Mel270, Omm1 and Omm2.3) were exposed to escalating concentrations of niclosamide for 72 h, and protein biomass was determined by sulforhodamine B assay. (C) UM cells were seeded in drug-free agarose culture and incubated for 14 days, colonies were counted. Clonogenicity was expressed by normalizing to control. (D) NOD/SCID mice bearing palpable Omm1 xenografted tumors were treated with vehicle (PBS) or p-niclosamide (25 mg/kg, i.p.) daily. The tumor volumes measured every other day versus time were plotted. Error bars, SD. **, p< 0.01; ***, p< 0.001, Student's t test. (E) Weights of tumors dissected on day 14 after treatment with p-niclosamide. Representative tumors are shown (top). Data (bottom) shown are the mean ± SD of tumor weights from each group. Vehicle (n=6), p-niclosamide (n=8). ***, p< 0.001, Student's t test. (F) Hematoxylin-eosin (H&E) staining and immnunohistochemical analysis with anti-Ki67 of xenograft tissues from mice sacrificed 14 days after p-niclosamide treatment (left). The total number of Ki67 positive cells (brown-stained nuclei, regardless of staining intensity were counted as positive) in 3 random microscopic fields were counted by Image-Pro Plus 6.0. Data (right) shown are the mean ± SD of Ki67 index from 3 random microscopic fields. ***, p< 0.001, Student's t test.