Figure 5.
Systemic injection of NSC-sTRAIL in combination with Lan C induces invasive glioblastoma (GBM) tumor regression in vivo. Mice were implanted with 2 × 104 GBM8 cells (~400 neurospheres) expressing Fluc and mCherry into the left forebrain. One and three weeks post-tumor cells implantation, mice received intravenous injection with 2 × 105 cells of either NSC-sTRAIL or NSC-Vluc (control) expressing Gluc. Each group of mice was divided into two subgroups which received an i.p. injection (three times per week over 4 weeks) of either DMSO or Lan C (1 mg/kg b.wt.). (A): In vivo Fluc bioluminescence imaging was performed once/week to monitor tumor growth. Representative images at 21, 28, and 35 days post-GBM cells implantation are shown. Pseudocolor represents radiance intensity of the tumors (photons/second per cm2 per surface radiance). (B): Tumor-associated photon counts were quantified using an IVIS imaging system software. Data presented as the mean of total flux of Fluc (photons/second) ± SD (n = 10; **, p <.01 vs. control; ##, p <.01 vs. Lan C alone by ANOVA and Tukey’s post hoc test). (C): H&E staining of representative brain sections the different treatment groups. (D): Kaplan-Meier survival curves of orthotopic GBM8 bearing athymic nude mice with different treatment strategies. *, p <.05 versus NSC-Vluc/Gluc + DMSO; **, p <.01, NSC-sTRAIL/Gluc + Lan C versus NSC-Vluc/Gluc + DMSO, NSC-Vluc/Gluc + Lan C, or NSC-sTRAIL/Gluc + DMSO. Abbreviations: DMSO, dimethyl sulfoxide; NSC, neural stem cell; TRAIL, tumor necrosis factor-related apoptosis-inducing ligand.