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- 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.
- Authors
YUNCHENG ZHANG; YUANWEN ZHENG; ALI FAHEEM; TIANTONG SUN; CHUNYOU LI; ZHE LI; DIANTANG ZHAO; CHAO WU; JUN LIU
- 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.
- Subjects
LIVER cancer; MTOR protein; PHOSPHATIDYLINOSITOL 3-kinases; PHOSPHORYLATION; PROTEIN kinase B; PROTEIN kinase inhibitors; GENETICS
- Publication
Oncology Letters, 2016, Vol 11, Issue 3, p1685
- ISSN
1792-1074
- Publication type
Article
- DOI
10.3892/ol.2016.4111