Figure 6.

Combined administration of ZSTK474 and J591PE induces regression of C4-2Luc prostate cancer tumors in nude mice. (A) Dynamics of luminescence of C4-2Luc tumors after a single local injection of DMSO, ZSTK474 (375 µg/kg), J591PE (2.5 mg/kg), or the combination of ZSTK474 and J591PE. Luminescence was monitored for 6 days by optical imaging and expressed as fold change compared to luminescence at day 0. Results are expressed as means ± SEM, n = 4 (DMSO) and n = 10 (ZSTK474, J591PE, combination). (B) Western blot analysis of C4-2Luc tumors excised 6 hours after injections of drugs. Combination of ZSTK474 and J591PE decreases MCL-1 protein levels and promotes apoptosis (increased c-caspase 3 and c-PARP) when compared to vehicle (DMSO). ZSTK474 alone or in combination with J591PE inhibits the phosphorylation of p-AKT (S⁴⁷³) and p-BAD (S¹¹²). Representative Western blots are shown. (C) Representative images of nude mice recorded on IVIS 100 luminescent imaging station showing ROI, 15 minutes after intraperitoneal (i.p.) luciferin injection. Representative images of background luminescence outside the tumors are shown in Figure W6C.