ABT-869 exhibits dose-dependent efficacy and regression of established subcutaneous MV-4-11 tumors. (A) Daily oral administration of ABT-869 at concentrations of 5, 10, 20 and 40 mg/kg/day was initiated when the MV-411 tumors reached an average of 400 mm3 in volume. The graph shows the dosage response to the inhibitor compared with tumors treated with vehicle control (3 mice per group). (B). Mice injected with MV-411 cells were treated with 40 mg/kg/day ABT-869 or vehicle the day after the injection of cells. The graph shows that the mice receiving treatment never developed tumors in contrast to the vehicle control (3 mice per group). (C) After a single administration of ABT-869 (10 mg/kg), tumors were harvested 3 and 6 hours later, snap-frozen in liquid N2, homogenized in lysis buffer, immunoprecipitated with anti-PY20, and analyzed by Western blot with anti-FLT3. (D) H&E sections of tumors from day 12 of dosing treated with vehicle or 40 mg/kg/d of ABT-869 at low (× 10) and high (× 40) power. Vehicle control–treated tumors show increased mitotic activity (arrowheads, lower left panel). Treated tumors show areas of cell death and inflammatory cells (arrowheads, lower right panel). (E) Ki67 and TUNEL staining of tumor sections from day 12 of dosing were used to evaluate proliferation and apoptosis, respectively.
