Fig. 6: The underlying mechanism of the synergistic anticancer effects of metformin/DNA nanocomplexes.

A Effects of different nanomaterial treatments on AKT/AMPK-mTOR pathways in H358 cells. B Effects of different nanomaterial treatments on AKT/AMPK-mTOR pathways in H23 cells. Analyses were performed as in Fig. 5F. Tumor tissues from NTMgK-, NTMF-, and NTMFK-treated mice were subjected to hematoxylin and eosin (H&E) staining and displayed visible nuclear shrinkage and vacuolization, indicating strong damage to the tumors. KRAS expression was notably decreased in NTMgK- and NTMFK-treated tissues, as shown in the middle panel of Fig. 5F. As expected, Ki67 staining was markedly reduced in NTMFK-treated tumors. These data suggested that both metformin and siRNA independently exert moderate anticancer effects. More importantly, NTMFK comprising metformin and siRNA had a stronger therapeutic effect in vivo than metformin or siRNA alone.