Figure 6.

Aurora kinase small-molecule inhibitor treatment of human melanoma xenograft-bearing nude mice. (A) Nude mice, bearing subcutaneous WM983-B MGP melanoma xenografts, received the first i.p. injection of Aurora kinase inhibitor (30 mg/kg) or Aurora kinase inhibitor followed 24 hours later by i.p. injection of paclitaxel (10 mg/kg) on the day (day 1) a tumor(s) had reached 5 mm in any direction. Subsequent i.p. injections were given on day 3, 7, 10, 14, 17, 21, and 24. Controls depicted show the fractional tumor volume of mice that were not injected or received only the Aurora kinase inhibitor delivery vehicle, DMSO. Tumor volumes for each of the 2 experimental arms are the mean of 3 animals each and for each of the control arms of 2 animals each. (B) WM983-B MGP melanoma xenografts received the first intratumoral injection of Aurora kinase A or Aurora kinase B antisense vector, or Aurora kinase B dead-kinase (DN) vector, each mixed with DC-Chol liposomes, on the day (day 1) a tumor(s) had reached 5 mm in any direction. Subsequent intratumoral injections were given on day 3, 7, 10, and 14. Tumors that did not receive intratumoral injections served as controls. (C) pHisH3 immunohistochemical analysis of tissue sections, prepared from WM983-B MGP melanoma xenografts of nude mice that as described in A were injected i.p. with the delivery vehicle DMSO (panel a), the Aurora kinase inhibitor (30 mg/kg) (panel b), or the Aurora kinase inhibitor (30 mg/kg) combined with paclitaxel (10 mg/kg) (panel c). The arrows in the melanoma xenograft tissue section depicted in panel a point to some of the pHisH3-positive cells. Tissue sections, prepared from WM983-B MGP melanoma xenografts of nude mice that were injected i.p. with the Aurora kinase inhibitor (30 mg/kg) combined with paclitaxel (10 mg/kg) (panel d) or that did not receive injections (panel e), were probed with an antibody to human Ki67. The tumor sections, depicted in panels a to e, were counterstained with hematoxylin.