Figure 4: Inhibiting miR-128-3p suppresses tumour growth and distant metastasis and reverses resistance of highly malignant NSCLC cells to chemotherapeutic drugs.

(a) A549-luc-control-sponge and A549-luc-miR-128-3p-sponge cells were, respectively, implanted in the inguinal folds of separate nude mice. On day 45, tumours were dissected and imaged as shown. A549-luc-CDDP-4th cells were subcutaneously implanted, followed by intravenous administration of control (NC) or miR-128-3p antagomirs (Anta), respectively. On day 30, tumours were dissected and imaged as shown. Bioluminescent images of subcutaneous tumours or/and spontaneous metastasis are shown. (b) A group of mice subcutaneously inoculated with vector-control A549-luc-CDDP4th cells were killed at day 30 after the initial inoculation, and a parallel group of mice were inoculated with A549-luc-CDDP4th cells stably silenced with miR-128-3p by the miR-128-3p sponge and killed for further analysis at day 60 after the initial inoculation. Bioluminescent images of subcutaneous tumours or/and spontaneous metastases are shown (left). Bright-field imaging and fluorescent visualization confirmed efficient inhibition of miR-128-3p by miRNA sponge strategy (right panel). Scale bar, 50 μm. (c) Bioluminescent images of subcutaneous tumours and spontaneous metastasis of A549-luc-miR-128-3p or LL/2-luc-M38 cells in response to CDDP treatment or its combination (Comb) with miR-128-3p antagomir (Anta). Corresponding residual tumours were dissected and imaged as shown. (d and e) In response to the indicated treatments, bioluminescent images of experimental distant metastasis of the indicated cells are shown. Lung metastases were histologically confirmed by H&E staining. Scale bar, 200 μm. (f) OS of mice in the experimental metastasis model receiving the indicated treatments. *P<0.05. (g) Cell viability assays determined the resistance or sensitivity to chemotherapeutic drugs including CDDP, gemcitabine (GEM) and paclitaxel (PAC), which administered, respectively, at a final concentration of 3, 0.5 and 1 μg ml⁻¹, were separately added to the indicated cells pretreated with 100 nM control (NC) or miR-128-3p antagomir (Anta). H&E, haematoxylin and eosin.