title: A novel AKT inhibitor, AZD5363, inhibits phosphorylation of AKT downstream molecules, and activates phosphorylation of mTOR and SMG-1 dependent on the liver cancer cell type.
abstract: Due to frequent phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway dysregulation, AKT is typically accepted as a promising anticancer therapeutic target. mTOR, in particular, represents a suitable therapeutic target for hepatocellular carcinoma, whilst suppressor with morphogenetic effect on genitalia family member-1 (SMG-1) is believed to serve a potential tumor suppressor role in human cancer. Despite SMG-1 and mTOR belonging to the same PI3K-related kinase family, the interactions between them are not yet fully understood. In the present study, a novel pyrrolopyrimidine-derived compound, AZD5363, was observed to suppress proliferation in liver cancer Hep-G2 and Huh-7 cells by inhibiting the phosphorylation of downstream molecules in the AKT signal pathway, in a dose- and time-dependent manner. AZD5363 activated the phosphorylation of mTOR, dependent on the liver cancer cell type, as it may have differing effects in various liver cancer cell lines. Additionally, AZD5363 also activated SMG-1 within the same liver cancer cells types, which subsequently activated the phosphorylation of mTOR. In conclusion, the present study indicates that AZD5363 inhibited phosphorylation of AKT downstream molecules, and activated phosphorylation of mTOR and SMG-1, dependent on the liver cancer type.
authors.affiliation: Department of Hepatobiliary Surgery and Center of Organ Transplantation, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Yuncheng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery and Center of Organ Transplantation, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Yuanwen
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Shandong University School of Medicine, Jinan, Shandong 250021, P.R. China.
authors.forename: Ali
authors.initials: A
authors.lastname: Faheem
authors.affiliation: Shandong University School of Medicine, Jinan, Shandong 250021, P.R. China.
authors.forename: Tiantong
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Hepatobiliary Surgery and Center of Organ Transplantation, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Chunyou
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery and Center of Organ Transplantation, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery and Center of Organ Transplantation, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Diantang
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Hepatobiliary Surgery and Center of Organ Transplantation, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Hepatobiliary Surgery and Center of Organ Transplantation, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
keywords: AKT; AZD5363; SMG-1; liver cancer; mTOR