MLN8237 induces inhibition of tumor growth in MM xenograft murine model. MM1.S cells were injected subcutaneously into SCID mice. After 2 weeks of tumor engraftment, mice were treated orally with vehicle or MLN8237 (7.5 mg/kg, 15 mg/kg, and 30 mg/kg) for 21 consecutive days. Tumor size, survival, and changes in weight were measured. (A) Tumor growth was significantly inhibited (t test, one-tailed distribution, P < .007). Mean tumor volumes (cubic millimeter [volume]) ± SD (n = 8-10 animals/group) are shown from the beginning of treatment. (B) The overall survival after the injection of tumor cells was significantly increased (log-rank, Mantel-Cox test, P < .03; log-rank test for trend, P < .005) in treated compared with control animals. (C) Treatment with MLN8237 was not associated with significant changes in weight (t test, one-tailed distribution, P = not significant). Mean weight (grams) ± SD (n = 8-10 animals/group) is shown from the beginning of treatment. (D) Induction of apoptosis and cell death in tumors excised from vehicle or MLN8237 (7.5 mg/kg, 15 mg/kg, and 30 mg/kg) treated animals are shown by TUNEL assay. Photomicrographs show apoptotic cells indicated by arrows (brown) with nucleus (blue; original magnification ×20) using light microscopy. The average number of TUNEL-positive cells was determined in 93 mm² area.