Fig. 2.

si-hVADC1 inhibition of tumor growth in vivo. (A) U-87MG cells were s.c. inoculated into nude mice. On day 13, the mice were divided into 2 groups and xenografts were injected every 3 days with si-NT (●, 8 mice) or si-hVDAC1 (▲, 16 mice) to a final concentration of 50–60nM (***P≤ .0001). (B) On day 33, the si-hVDAC-treated mice were subdivided into 2 groups (8 mice each). One group (▲) continued si-hVDAC1 treatment, the other switched to si-NT (○) treatment. si-NT-TTs and si-hVDAC1-TTs sections stained for VDAC1 by IHC (C) or immunoblot (D). RU = average relative units. (E) Orthotopic GBM, MRI of brains 33 days post-engraftment with U-87MG cells treated with si-NT or si-VDAC1. (F) Calculated tumor volume after 22 (black bars) and 33 days (gray bars). Results = mean ± SEM (n = 4–5), ****P ≤ .0001. (G) MRI of brains engrafted with U-87MG cells, 22 days after cell engraftment and treatment start. Two days post-engraftment, the mice were divided into 2 groups (6 mice each) and injected i.v. every 3 days with 100 μL of si-NT- or si-hVDAC-encapsulated-PLGA nanoparticles (400 nM siRNA). (H) Calculated tumor volume after 20 and 30 days. Red and black bars representing tumor volume of mice treated with si-NT- or si-hVDAC-encapsulated PLGA nanoparticles, respectively. Results = mean ± SEM (n = 6), *P ≤ .05; **P ≤ .01. (I) Mice survival over time of si-NT-PLGA- (red line) and si-hVDAC1-PLGA nanoparticle (black line) treated mice is presented in the cumulative Kaplan–Meier survival curves. ***P ≤ .001. (J) Orthotopic MZ-18 cells (10 × 10⁴) (PDX) were engrafted into mice brains and 2 days later, the mice were divided into 2 groups (6 mice each) and injected i.v. every 3 days with si-NT- (black bars) or si-hVDAC (gray bars)-encapsulated PLGA-PEI nanoparticles (400 nM siRNA). Tumor volume was calculated from MRI taken 34 days post cell engraftment, and then 10 days after treatment termination (day 45).