FOXO3 and non-small cell lung carcinoma: In conclusion, the present study for the first time demonstrated that DHW-221, as a PI3K/mTOR dual inhibitor and novel P-gp inhibitor, exerts potent cytotoxic activity and induces cell apoptosis to overcome MDR through Akt-mediated FOXO3a nuclear translocation in NSCLC (Figure 8C, made in https://app.biorender.com/) both in vitro and in vivo.