PMID- 26427150
OWN - NLM
STAT- MEDLINE
DCOM- 20151026
LR  - 20231213
IS  - 1433-6510 (Print)
IS  - 1433-6510 (Linking)
VI  - 61
IP  - 8
DP  - 2015
TI  - Inhibition of Autophagy Increases Proliferation Inhibition and Apoptosis Induced 
      by the PI3K/mTOR Inhibitor NVP-BEZ235 in Breast Cancer Cells.
PG  - 1043-51
AB  - BACKGROUND: The phosphoinositide 3 kinase (PI3K)/AKT/mammalian target of the 
      rapamycin (mTOR) pathway is a complicated intracellular pathway which leads to 
      cell growth and tumor proliferation and plays a significant role in breast 
      cancer. Multiple compounds targeting this pathway are being evaluated in clinical 
      trials. NVP-BEZ235, a novel and orally available dual PI3K/mTOR inhibitor, showed 
      great antitumor effect and provided a therapy strategy in breast cancer. METHODS: 
      In this study, we detect the effect of NVP-BEZ235 on cell viability, apoptosis, 
      and autophagy in a breast cancer cell line. We also test the effect of NVP-BEZ235 
      on the expression of PI3K/AKT/mTOR pathway proteins p-AKT, p-mTOR, and p-70S6K. 
      RESULTS: The results showed that the PI3K/AKT/mTOR proteins p-AKT, p-mTOR, and 
      p-70S6K were obviously suppressed by NVP-BEZ235. NVP-BEZ235 inhibited cell 
      proliferation and induced apoptosis and autophagy in breast cancer cells. In 
      combination with autophagy inhibitors or autophagy gene knockdown, enhanced 
      growth inhibition and apoptosis was induced by NVP-BEZ235 in MCF-7 cells. 
      CONCLUSIONS: This study provides a novel treatment strategy that PI3K/AKT/mTOR 
      pathway inhibitors in combination with autophagy inhibitors lead to further 
      apoptosis in breast cancer cells.
FAU - Ji, Yinghua
AU  - Ji Y
FAU - Di, Wenyu
AU  - Di W
FAU - Yang, Qinghui
AU  - Yang Q
FAU - Lu, Zhihong
AU  - Lu Z
FAU - Cai, Weimei
AU  - Cai W
FAU - Wu, Jieqing
AU  - Wu J
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Clin Lab
JT  - Clinical laboratory
JID - 9705611
RN  - 0 (Imidazoles)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Quinolines)
RN  - 5142-23-4 (3-methyladenine)
RN  - 886U3H6UFF (Chloroquine)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
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 6.2.1.45 (ATG7 protein, human)
RN  - EC 6.2.1.45 (Autophagy-Related Protein 7)
RN  - EC 6.2.1.45 (Ubiquitin-Activating Enzymes)
RN  - JAC85A2161 (Adenine)
RN  - RUJ6Z9Y0DT (dactolisib)
SB  - IM
MH  - Adenine/analogs & derivatives/pharmacology
MH  - Antineoplastic Combined Chemotherapy Protocols/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Autophagy/*drug effects
MH  - Autophagy-Related Protein 7
MH  - Breast Neoplasms/*enzymology/genetics/pathology
MH  - Cell Proliferation/*drug effects
MH  - Cell Survival/drug effects
MH  - Chloroquine/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - MCF-7 Cells
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Quinolines/pharmacology
MH  - RNA Interference
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - Time Factors
MH  - Transfection
MH  - Ubiquitin-Activating Enzymes/genetics/metabolism
EDAT- 2015/10/03 06:00
MHDA- 2015/10/27 06:00
CRDT- 2015/10/03 06:00
PHST- 2015/10/03 06:00 [entrez]
PHST- 2015/10/03 06:00 [pubmed]
PHST- 2015/10/27 06:00 [medline]
AID - 10.7754/clin.lab.2015.150144 [doi]
PST - ppublish
SO  - Clin Lab. 2015;61(8):1043-51. doi: 10.7754/clin.lab.2015.150144.