PMID- 27793908
OWN - NLM
STAT- MEDLINE
DCOM- 20170131
LR  - 20191210
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 36
IP  - 11
DP  - 2016 Nov
TI  - Co-treatment of LY294002 or MK-2206 with AZD5363 Attenuates AZD5363-induced 
      Increase in the Level of Phosphorylated AKT.
PG  - 5849-5858
AB  - Clinical trials are in progress on AZD5363, an inhibitor of protein kinase B 
      (AKT), to assess its effects on the phosphoinositide 3-kinase 
      (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. Cells treated with AKT 
      inhibitors have been reported to activate alternative pathways in order to escape 
      growth inhibition. AZD5363-sensitized Hs578T breast cancer cells displayed 
      reduced levels of phosphorylated glycogen synthase kinase 3 beta (pGSK3beta). 
      Interestingly, in AZD5363-treated cells, the level of phosphorylated (activated) 
      AKT (pAKT) increased. Since pAKT positively correlates with cancer growth and 
      survival, we aimed to identify conditions that could reduce AZD5363-induction of 
      pAKT. We examined whether AZD5363 induction of pAKT could be reduced by 
      co-treatment with inhibitors of the PI3K/AKT/mTOR pathway (LY294002, MK-2206, 
      wortmannin, perifosine, rapamycin, everolimus, and temsirolimus). We observed 
      that co-treatment of LY294002 or MK-2206 with AZD5363 reduced the level of pAKT. 
      Since MK-2206 is clinically used, we propose that co-treatment using MK-2206 with 
      AZD5363 would prove beneficial in blocking the AZD5363-induced pAKT signaling 
      pathway. Our findings contribute to the development of AZD5363-based 
      sensitization therapies for patients with cancer.
CI  - Copyright(c) 2016 International Institute of Anticancer Research (Dr. John G. 
      Delinassios), All rights reserved.
FAU - Choi, Ae-Ran
AU  - Choi AR
AD  - Research Institute, National Cancer Center, Goyang-si, Republic of Korea.
FAU - Kim, Ju-Hwa
AU  - Kim JH
AD  - Research Institute, National Cancer Center, Goyang-si, Republic of Korea.
FAU - Woo, Yeon Hwa
AU  - Woo YH
AD  - Research Institute, National Cancer Center, Goyang-si, Republic of Korea.
FAU - Cheon, Ji Hyun
AU  - Cheon JH
AD  - School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
FAU - Kim, Hyung Sik
AU  - Kim HS
AD  - School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea 
      hkims@skku.edu syoon88@gmail.com.
FAU - Yoon, Sungpil
AU  - Yoon S
AD  - Research Institute, National Cancer Center, Goyang-si, Republic of Korea 
      hkims@skku.edu syoon88@gmail.com.
AD  - School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Chromones)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Heterocyclic Compounds, 3-Ring)
RN  - 0 (MK 2206)
RN  - 0 (Morpholines)
RN  - 0 (Pyrimidines)
RN  - 0 (Pyrroles)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - WFR23M21IE (capivasertib)
SB  - IM
MH  - Breast Neoplasms/metabolism/pathology
MH  - Cell Line, Tumor
MH  - Chromones
MH  - Drug Synergism
MH  - Enzyme Inhibitors/*pharmacology
MH  - Heterocyclic Compounds, 3-Ring/*pharmacology
MH  - Humans
MH  - Morpholines
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Pyrimidines/*pharmacology
MH  - Pyrroles/*pharmacology
OTO - NOTNLM
OT  - AZD5363
OT  - LY294002
OT  - MK-2206
OT  - PI3K/AKT/mTOR
OT  - pAkt
EDAT- 2016/10/30 06:00
MHDA- 2017/02/01 06:00
CRDT- 2016/10/30 06:00
PHST- 2016/02/19 00:00 [received]
PHST- 2016/04/11 00:00 [accepted]
PHST- 2016/10/30 06:00 [pubmed]
PHST- 2017/02/01 06:00 [medline]
PHST- 2016/10/30 06:00 [entrez]
AID - 36/11/5849 [pii]
AID - 10.21873/anticanres.11170 [doi]
PST - ppublish
SO  - Anticancer Res. 2016 Nov;36(11):5849-5858. doi: 10.21873/anticanres.11170.