Moxidectin induces lethal autophagy arrest via CFTR

Abstract Colorectal cancer (CRC) is a cancer with a high morbidity and mortality worldwide. Hence， developing new therapeutic drugs for CRC is very important. Moxidectin (MOX) has shown good anti-glioblastoma effect both in vitro and in vivo, This study aimed to elucidate the anti-CRC effect of MOX and its potential mechanism. By investigating the influence of MOX on the viability, apoptosis, necrosis and autophagy of colorectal cancer cells (HCT15 and SW620) and its underlying mechanisms. It was found that MOX can induce autophagy arrest, promote autophagy initiation, inhibit autophagic flux and cell proliferation, simultaneously PI3K-Akt-mTOR signaling pathway and microtubule acetylation. Furthermore, MOX suppressed the growth of xenograft tumors, which was consistent with the in vitro results.