Fig. 6. Therapeutic efficacy in the p53-null orthotopic HCC tumors and the liver metastases of p53-null NSCLC.
(A) Scheme of tumor inoculation and different treatments in luciferase-expressing Hep3B (Hep3B-Luc) orthotopic tumor–bearing nude mice. Twenty-one days after tumor inoculation, mice were treated with PBS (intravenous), EGFP-mRNA NPs (intravenous), p53-mRNA NPs (intravenous), everolimus (oral), or p53-mRNA NPs (intravenous) + everolimus (oral) every 3 days for four rounds (mRNA dose, 750 μg/kg; everolimus dose, 5 mg/kg). (B) Bioluminescence images of the Hep3B-Luc orthotopic tumor–bearing nude mice at days 0, 6, and 12. (C) Average radiance [×106 photons per second (s) per cm2 per steradian (sr)] of tumor burden determined by bioluminescence imaging at different time points. (D) Average radiance of tumor burden at the endpoint (day 12). Data shown as means ± SEM (n = 3), and statistical significance was determined using two-tailed t test (*P < 0.05, **P < 0.01). (E) Scheme of tumor inoculation and different treatments in p53-null H1299 metastatic tumor–bearing nude mice. Twenty-eight days after tumor inoculation, mice were treated with PBS (intravenous), EGFP-mRNA NPs (intravenous), p53-mRNA NPs (intravenous), everolimus (oral), or p53-mRNA NPs (intravenous) + everolimus (oral) every 3 days for five rounds (mRNA dose, 750 μg/kg; everolimus dose, 5 mg/kg). Organs from different groups were harvested three days after the final treatment. (F) Histological examination of liver tissues from each group by H&E staining. The metastatic lesions (red dotted ovals) were identified as cell clusters with darkly stained nuclei. Scale bars, 100 μm. (G) The number of metastatic nodules in the liver from each group. One liver was randomly selected from each group with a blind method, and the liver section from each group was divided into four regions for counting of the metastasis nodules. Data shown as means ± SEM (n = 4 regions), and statistical significance was determined using two-tailed t test (*P < 0.05, **P < 0.01).