Figure 4
Ganetespib inhibits progenitor self-renewal and GEMM tumor progression. (A) PCAP cell lines embedded in Matrigel® were untreated or treated with 16 nM ganetespib for seven days and organoids > 50 μm were enumerated (n = 3, P < 0.05). (B) Primary tumor from intact or DGX-treated mice luminal (CD133+) organoids were untreated or treated in vitro with 16 nM ganetespib for seven days and sphere numbers determined (n = 3, P < 0.05). (C) Representative images of CD133+ organoid cultures following 7 days in the presence or absence of ganetespib (scale bars = 200 μm). (D) Tumor weights from PB-Cre4 Ptenfl/fl;Tp53fl/fl GEMM mice drugged intravenously with 125 mg/kg ganetespib (n = 6) or DMSO (n = 3) once a week for eight weeks. Data presented as average tumor weight + /− SEM (P < 0.05). (E,F) Representative photomicrographs of untreated (E) and ganetespib-treated (F) Ptenfl/fl;Tp53fl/fl GEMM mouse prostates (Hematoxylin and eosin stain, scale bar = 50 µm). Arrows identify stromal invasion. Asterisk indicates a magnified region of tissue. (G) Western blot analysis of individual PB-Cre4 Ptenfl/fl;Tp53fl/fl mouse tumor lysates either untreated or following 24 or 48 hours after intravenous ganetespib application. Control and treated samples were run on the same gel but cropped for convenient visualization.
