PMID- 22995071
OWN - NLM
STAT- MEDLINE
DCOM- 20130424
LR  - 20190221
IS  - 1872-7980 (Electronic)
IS  - 0304-3835 (Linking)
VI  - 329
IP  - 1
DP  - 2013 Feb 1
TI  - Low dose histone deacetylase inhibitor, LBH589, potentiates anticancer effect of 
      docetaxel in epithelial ovarian cancer via PI3K/Akt pathway in vitro.
PG  - 17-26
LID - S0304-3835(12)00540-X [pii]
LID - 10.1016/j.canlet.2012.08.035 [doi]
AB  - The purpose of this study was to investigate the effect of combination of LBH589 
      with docetaxel (DTX) on the growth and survival of epithelial ovarian cancer 
      (EOC) cells in vitro and the possible mechanisms of chemo-sensitization of LBH589 
      in the combination treatment. The effect of LBH589 alone or in combination with 
      DTX on four EOC cell lines (OVCAR-3, IGROV-1, A2780 and SKOV-3) was studied by 
      MTT and clonogenic assays, acridine orange (AO)/ethidium bromide (EB) staining 
      for apoptosis, Western blotting for apoptosis-related proteins, histone H3 and H4 
      proteins, DNA double strand break (DSB) repair marker and phosphorylation of Akt. 
      LBH589 alone inhibited EOC cell proliferation in a time and dose-dependent 
      manner. Low-dose of LBH589 (IC(20)) combined with DTX had an additive effect and 
      greatly improved efficacy of DTX cell killing in EOC cells. Compared to DTX 
      alone, the combination treatment with LBH589 and DTX induced more apoptosis and 
      led to an increased and persistent DSB. Cell death following single or combined 
      treatment was associated with the release of cytochrome c activity, increased 
      caspase-3 (active) and PARP-1(cleaved), histone acetylation-related proteins and 
      PI3k/Akt signaling pathway. Our results suggest that LBH589 enhances DTX-induced 
      apoptosis in human EOC cells, and can be used in combination with DTX as an 
      attractive strategy for treating human EOC.
CI  - Copyright (c) 2012 Elsevier Ireland Ltd. All rights reserved.
FAU - Chao, Hongtu
AU  - Chao H
AD  - Department of Gynecologic Oncology, Henan Cancer Hospital, Zhengzhou University, 
      Zhengzhou, Henan, China.
FAU - Wang, Li
AU  - Wang L
FAU - Hao, Jingli
AU  - Hao J
FAU - Ni, Jie
AU  - Ni J
FAU - Chang, Lei
AU  - Chang L
FAU - Graham, Peter H
AU  - Graham PH
FAU - Kearsley, John H
AU  - Kearsley JH
FAU - Li, Yong
AU  - Li Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120918
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Histones)
RN  - 0 (Hydroxamic Acids)
RN  - 0 (Indoles)
RN  - 0 (Taxoids)
RN  - 15H5577CQD (Docetaxel)
RN  - 9647FM7Y3Z (Panobinostat)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/*pharmacology
MH  - Apoptosis/drug effects
MH  - Carcinoma, Ovarian Epithelial
MH  - Caspase 3/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - DNA Repair/drug effects
MH  - Docetaxel
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Histone Deacetylase Inhibitors/administration & dosage/*pharmacology
MH  - Histones/metabolism
MH  - Humans
MH  - Hydroxamic Acids/administration & dosage/*pharmacology
MH  - Indoles/administration & dosage/*pharmacology
MH  - Neoplasms, Glandular and Epithelial/*drug therapy/metabolism/pathology
MH  - Ovarian Neoplasms/*drug therapy/metabolism/pathology
MH  - Panobinostat
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Signal Transduction/drug effects
MH  - Taxoids/administration & dosage/*pharmacology
EDAT- 2012/09/22 06:00
MHDA- 2013/04/25 06:00
CRDT- 2012/09/22 06:00
PHST- 2012/03/20 00:00 [received]
PHST- 2012/08/29 00:00 [revised]
PHST- 2012/08/31 00:00 [accepted]
PHST- 2012/09/22 06:00 [entrez]
PHST- 2012/09/22 06:00 [pubmed]
PHST- 2013/04/25 06:00 [medline]
AID - S0304-3835(12)00540-X [pii]
AID - 10.1016/j.canlet.2012.08.035 [doi]
PST - ppublish
SO  - Cancer Lett. 2013 Feb 1;329(1):17-26. doi: 10.1016/j.canlet.2012.08.035. Epub 
      2012 Sep 18.