PMID- 23006739
OWN - NLM
STAT- MEDLINE
DCOM- 20130509
LR  - 20211203
IS  - 1421-9794 (Electronic)
IS  - 0009-3157 (Linking)
VI  - 58
IP  - 4
DP  - 2012
TI  - The antitumor effect of GDC-0941 alone and in combination with rapamycin in 
      breast cancer cells.
PG  - 273-81
LID - 10.1159/000341812 [doi]
AB  - BACKGROUND: The phosphatidylinositide 3-kinase (PI3K)/Akt/mammalian target of 
      rapamycin (mTOR) pathway is a key potential target in breast cancer therapy. 
      Because some cancer cell lines are resistant to mTOR inhibition, we combined the 
      mTOR inhibitor with the PI3K inhibitor and assayed the inhibitory effect of this 
      combination versus that of a single inhibitor. METHODS: The proliferation of 
      MCF7, SK-BR-3, T-47D, and MDA-MB-231 cells was measured by MTT assay in the 
      presence of GDC-0941 and/or rapamycin. Afterwards, we determined the visible 
      changes in signaling in the PI3K/AKT/mTOR pathway by Western blotting. RESULTS: 
      GDC-0941 exhibited excellent inhibition on MCF7, T-47D and SK-BR-3 cells with 
      different characteristics. In addition, GDC-0941 blocked the feedback of PI3K/Akt 
      through S6K1, resulting in decreased Akt activity by rapamycin activation. The 
      combination of GDC-0941 and rapamycin downregulated the key components of the 
      cell cycle machinery, such as cyclin D1 and upregulated the apoptotic markers. 
      CONCLUSION: Our findings suggest that GDC-0941, either alone or in combination 
      with rapamycin, may serve as a new, promising approach for breast cancer 
      treatment.
CI  - Copyright (c) 2012 S. Karger AG, Basel.
FAU - Zheng, Jie
AU  - Zheng J
AD  - Department of Pathology, Jingmen First People's Hospital, Jingmen City, Hubei, 
      People's Republic of China. zhengjie9803@163.com
FAU - Zou, Xianjin
AU  - Zou X
FAU - Yao, Jia
AU  - Yao J
LA  - eng
PT  - Journal Article
DEP - 20120921
PL  - Switzerland
TA  - Chemotherapy
JT  - Chemotherapy
JID - 0144731
RN  - 0 
      (2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine)
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Indazoles)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Sulfonamides)
RN  - 136601-57-5 (Cyclin D1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (ribosomal protein S6 kinase, 70kD, polypeptide 1)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Antibiotics, Antineoplastic/*pharmacology
MH  - Breast Neoplasms/metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/*drug effects
MH  - Cyclin D1/metabolism
MH  - Down-Regulation/drug effects
MH  - Female
MH  - Humans
MH  - Indazoles/*pharmacology
MH  - MCF-7 Cells
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Signal Transduction/drug effects
MH  - Sirolimus/*pharmacology
MH  - Sulfonamides/*pharmacology
MH  - TOR Serine-Threonine Kinases/metabolism
EDAT- 2012/09/26 06:00
MHDA- 2013/05/10 06:00
CRDT- 2012/09/26 06:00
PHST- 2012/02/06 00:00 [received]
PHST- 2012/07/10 00:00 [accepted]
PHST- 2012/09/26 06:00 [entrez]
PHST- 2012/09/26 06:00 [pubmed]
PHST- 2013/05/10 06:00 [medline]
AID - 000341812 [pii]
AID - 10.1159/000341812 [doi]
PST - ppublish
SO  - Chemotherapy. 2012;58(4):273-81. doi: 10.1159/000341812. Epub 2012 Sep 21.