AZD6244 inhibits human plasmacytoma growth and prolongs survival in a murine xenograft model. (A) OPM1 MM cells were injected subcutaneously. Mice (n = 8 per group) received AZD6244 (orally twice per day) or control vehicle (cnt, ■) orally starting on day 1 for 9 days. Significant growth inhibition of OPM1 MM cells was noted in AZD6244-treated (◇ 25 mg/kg, ○ 50 mg/kg) compared with vehicle-treated control mice (n = 8; P = .03). Points indicate mean; bars, SE. (B) After OPM1 tumors were measurable, mice were treated with AZD6244 (25 mg/kg, — — —; 50 mg/kg, — - - —) or with control vehicle alone (cnt, —) for 9 consecutive days. Survival was evaluated from the first day of treatment until death or sacrifice (mice were killed when tumors reached 2 cm3 in diameter) using the SigmaPlot (Systat) analysis software (P = .02). (C) Representative immunohistochemical staining for phosphorylation of ERK (pERK) in tumor sections from vehicle control- and AZD6244 (25 mg/kg)–treated mice; original magnification × 100. See “Patients, materials, and methods; Immunohistochemistry” for more information on image acquisition. (D) Tumor tissues from mice treated with vehicle control or AZD6244 (25 mg/kg) for 1 day were harvested and processed, and lysates were subjected to immunoblotting using pERK and ERK Ab.
