Colorectal cancer is a major contributor of cancer-related mortality. The 
mammalian target or rapamycin (mTOR) signaling is frequently hyper-activated in 
colorectal cancers, promoting cancer progression and chemo-resistance. In the 
current study, we investigated the anti-colorectal cancer effect of a novel mTOR 
complex 1 (mTORC1) and mTORC2 dual inhibitor: AZD-2014. In cultured colorectal 
cancer cell lines, AZD-2014 significantly inhibited cancer cell growth without 
inducing significant cell apoptosis. AZD-2014 blocked activation of both mTORC1 
(S6K and S6 phosphorylation) and mTORC2 (Akt Ser 473 phosphorylation), and 
activated autophagy in colorectal cancer cells. Meanwhile, autophagy inhibition 
by 3-methyaldenine (3-MA) and hydroxychloroquine, as well as by siRNA knocking 
down of Beclin-1 or ATG-7, inhibited AZD-2014-induced cytotoxicity, while the 
apoptosis inhibitor had no rescue effect. In vivo, AZD-2014 oral administration 
significantly inhibited the growth of HT-29 cell xenograft in SCID mice, and the 
mice survival was dramatically improved. At the same time, in xenografted tumors 
administrated with AZD-2014, the activation of mTORC1 and mTORC2 were largely 
inhibited, and autophagic markers were significantly increased. Thus, AZD-2014 
inhibits colorectal cancer cell growth both in vivo and in vitro. Our results 
suggest that AZD-2014 may be further investigated for colorectal cancer therapy 
in clinical trials.