Induction of ASK1 reduces MM cell proliferation and prolongs survival in an MM xenograft model. (A) Induction of ASK1 inhibits MM cell proliferation. Luciferase-expressing ASK1-inducible IM9 transfectant (ASK1) or control TRE transfectant (TRE) were intravenously injected into sublethally irradiated SCID mice. Xenografted mice were orally administrated doxycycline (+Dox) by gavage (1 mg in 1 mL per mouse) and in drinking water (0.2 mg/mL Dox) at 6 days after engraftment or left untreated (−Dox). Bioluminescence was measured after injection with D-luciferin intraperitoneally on the days indicated, followed by image acquisition. Thirteen mice were used for each group. Data were acquired for individual mice that received a xenograft, and the horizontal bars indicate the median of each group. (B-C) Induction of ASK1 prolongs animal survival. Kaplan-Meier survival curve of mice engrafted with luciferase-expressing ASK1-inducible IM9 transfectants (B) or luciferase-expressing ASK1-inducible H929 transfectants (C). (D) Induction of ASK1 increases apoptosis of MM cells in vivo. Paraffin-embedded lung sections from luciferase-expressing ASK1-inducible–engrafted mice or control TRE H929 transfectant–engrafted mice treated with or without Dox at 20 days after engraftment were subjected to TUNEL assay. *P < .05, **P < .01, ***P < .001.