Figure 4. Acute exposure to CBL0137 attenuates GSCs self-renewal and tumor initiation.
A, For in vitro extreme limiting dilution assays (eLDA), GSCs were pretreated with vehicle (DMSO), 300 nM or 600 nM CBL0137 for 24 h before plating. Fourteen days later, each well was evaluated for the presence or absence of tumor spheres. Estimated stem cell frequencies for each condition are indicated. P-values indicate significance of differences in stem cell frequencies between groups (chi-square test). B–C, CBL0137 reduces tumor-initiating capacity of GSCs in vivo. 10 x 103 of viable cells were intracranially (IC) implanted. The Kaplan–Meier survival curves post-intracranial implantation of GSCs are shown [P=0.005 with log-rank analysis]. B, For ex vivo treatment, GSCs (specimen 387) were pre-treated for 24 h with vehicle (DMSO) or 300 nM CBL0137 prior to IC implantation (n=5 per group). C, For in vivo treatment, 7 d after IC implantation (specimen 3691), mice receive vehicle or CBL0137 (0.5 mg/mL) orally ad libitum by addition of drug to drinking water, which was replaced every 7 d (n=10 per group).