Fig. 5. Targeted replacement of miR-34a via FolamiR reduces tumor size in a murine model of lung adenocarcinoma.
(A) MRI-measured tumor burden after FolamiR-34a treatment (FolamiR-NC, n = 3; FolamiR-34a, n = 5). Error bars represent means ± SEM. **P < 0.01, two-way ANOVA and Bonferroni post hoc tests. Arrows represent treatment times (0.8 mg/kg, 1 nmol intravenous injection; total 10). (B) Representative three-dimensional volume renderings of the lungs and MRI images of the thoracic region of mice treated with FolamiRs during (day 8) and at the end of treatment (day 29). (C) Tumor/whole lung volume ratios from (B) at the indicated times showing the percentage of lung volume occupied by tumors. Error bars represent means ± SD. *P < 0.05, one-way ANOVA. (D) Representative H&E-stained tissue of the left lobe of the lung from animals from each treatment group (FolamiR-NC, FolamiR-34a). Scale bars, 1 mm. (E) Overall tumor burden calculated from total tumor area averaged from three histological sections obtained from each treated animal relative to the total area of the lung. Bars indicate the median. FolamiR-NC: n = 3, FolamiR-34a: n = 5; unpaired t test. (F) miR-34a target genes (Met, Myc, and Bcl-2) evaluated by qRT-PCR of tumor tissue normalized to Actin and graphed relative to FolamiR-NC–treated tumors (FolamiR-NC: n = 3, FolamiR-34a: n = 5). Error bars represent means ± SD. *P < 0.05, unpaired t test.