PMID- 21725613
OWN - NLM
STAT- MEDLINE
DCOM- 20120301
LR  - 20211203
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 26
IP  - 5
DP  - 2011 Nov
TI  - Growth inhibition by NVP-BEZ235, a dual PI3K/mTOR inhibitor, in hepatocellular 
      carcinoma cell lines.
PG  - 1273-9
LID - 10.3892/or.2011.1370 [doi]
AB  - Dysregulation of the phosphatidylinositol-3-kinase (PI3K)/mammalian target of 
      rapamycin (mTOR) pathway frequently occurs in human tumors, and is therefore 
      considered to be a good molecular target for treatment. In hepatocellular 
      carcinoma (HCC), overexpression of p-Akt and decrease of PTEN expression have 
      been reported. NVP-BEZ235 is a novel dual inhibitor of PI3K and mTOR; however, 
      its effect on HCC has not been documented. Consequently, we investigated the 
      effects of NVP-BEZ235 on the PLC/PRF/5, HLE, JHH7 and HepG2 HCC cell lines in 
      vitro and in vivo. NVP-BEZ235 decreased the levels of p-Akt and p-p70S6K and 
      inhibited cell proliferation in all HCC cell lines in a dose-dependent manner. 
      Flow cytometric analysis revealed that inhibition of cell proliferation by 
      NVP-BEZ235 was accompanied by G1 arrest in all cell lines, and that NVP-BEZ235 
      induced apoptosis in PLC/PRF/5 and HLE cells. Tumor growth was suppressed without 
      body weight loss when NVP-BEZ235 was orally administered to JHH-7 tumor-bearing 
      mice for 11 days. These results suggest that NVP-BEZ235 is a potential new 
      candidate for targeted HCC therapy.
FAU - Masuda, Mitsuhiro
AU  - Masuda M
AD  - Section for Cancer Immunotherapy, Investigative Treatment Division, Research 
      Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, 
      Chiba, Japan.
FAU - Shimomura, Manami
AU  - Shimomura M
FAU - Kobayashi, Ken
AU  - Kobayashi K
FAU - Kojima, Shuji
AU  - Kojima S
FAU - Nakatsura, Tetsuya
AU  - Nakatsura T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110701
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Imidazoles)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Quinolines)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - RUJ6Z9Y0DT (dactolisib)
SB  - IM
MH  - Animals
MH  - Carcinoma, Hepatocellular/*drug therapy/genetics/metabolism/pathology
MH  - Cell Growth Processes/drug effects
MH  - Cell Line, Tumor
MH  - Female
MH  - Humans
MH  - Imidazoles/*pharmacology
MH  - Liver Neoplasms/*drug therapy/genetics/metabolism/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Phosphatidylinositol 3-Kinase/genetics/metabolism
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Quinolines/*pharmacology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - Xenograft Model Antitumor Assays
EDAT- 2011/07/05 06:00
MHDA- 2012/03/02 06:00
CRDT- 2011/07/05 06:00
PHST- 2011/05/17 00:00 [received]
PHST- 2011/06/16 00:00 [accepted]
PHST- 2011/07/05 06:00 [entrez]
PHST- 2011/07/05 06:00 [pubmed]
PHST- 2012/03/02 06:00 [medline]
AID - 10.3892/or.2011.1370 [doi]
PST - ppublish
SO  - Oncol Rep. 2011 Nov;26(5):1273-9. doi: 10.3892/or.2011.1370. Epub 2011 Jul 1.