PMID- 30962658
OWN - NLM
STAT- MEDLINE
DCOM- 20190726
LR  - 20211204
IS  - 2186-3326 (Electronic)
IS  - 0027-7622 (Print)
IS  - 0027-7622 (Linking)
VI  - 81
IP  - 1
DP  - 2019 Feb
TI  - Enhanced efficacy of histone deacetylase inhibitor panobinostat combined with 
      dual PI3K/mTOR inhibitor BEZ235 against glioblastoma.
PG  - 93-102
LID - 10.18999/nagjms.81.1.93 [doi]
AB  - Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. 
      Despite multiple treatment strategies, the prognosis is still poor. This study 
      aimed to evaluate the efficacy of combination treatment of GBM with the histone 
      deacetylase (HDAC) inhibitor panobinostat and dual phosphoinositide 3-kinase 
      (PI3K) and mammalian target of rapamycin (mTOR) inhibitor BEZ235. GBM cells were 
      exposed to panobinostat and BEZ235 treatment alone or in combination, after which 
      cell viability, proliferation and apoptosis were detected. Furthermore, the 
      inhibitory mechanisms were investigated by Caspase-Glo assay, Western blot and 
      qPCR analysis. We found that combination treatment with panobinostat and BEZ235 
      synergistically inhibited cell viability, markedly inhibited cell proliferation 
      and induced apoptosis in GBM cells. Mechanistically, cotreatment with 
      panobinostat and BEZ235 increased caspase 3/7 activity, suppressed proliferation- 
      and antiapoptosis-related markers and AKT signaling in GBM cells. Cotreatment 
      with panobinostat and BEZ235 warrants further evaluation in GBM therapy.
FAU - Meng, Wei
AU  - Meng W
AD  - Department of Pediatric Neurosurgery, Xin Hua Hospital, Affiliated with Shanghai 
      Jiao Tong University School of Medicine, Shanghai, China.
FAU - Wang, Baocheng
AU  - Wang B
AD  - Department of Pediatric Neurosurgery, Xin Hua Hospital, Affiliated with Shanghai 
      Jiao Tong University School of Medicine, Shanghai, China.
FAU - Mao, Weiwei
AU  - Mao W
AD  - Department of Pediatric Neurosurgery, Xin Hua Hospital, Affiliated with Shanghai 
      Jiao Tong University School of Medicine, Shanghai, China.
FAU - Wang, Jiajia
AU  - Wang J
AD  - Department of Pediatric Neurosurgery, Xin Hua Hospital, Affiliated with Shanghai 
      Jiao Tong University School of Medicine, Shanghai, China.
FAU - Zhao, Yang
AU  - Zhao Y
AD  - Department of Pediatric Neurosurgery, Xin Hua Hospital, Affiliated with Shanghai 
      Jiao Tong University School of Medicine, Shanghai, China.
FAU - Li, Qifeng
AU  - Li Q
AD  - Department of Pediatric Neurosurgery, Xin Hua Hospital, Affiliated with Shanghai 
      Jiao Tong University School of Medicine, Shanghai, China.
FAU - Zhang, Chenran
AU  - Zhang C
AD  - Department of Pediatric Neurosurgery, Xin Hua Hospital, Affiliated with Shanghai 
      Jiao Tong University School of Medicine, Shanghai, China.
FAU - Ma, Jie
AU  - Ma J
AD  - Department of Pediatric Neurosurgery, Xin Hua Hospital, Affiliated with Shanghai 
      Jiao Tong University School of Medicine, Shanghai, China.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Nagoya J Med Sci
JT  - Nagoya journal of medical science
JID - 0412011
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (Quinolines)
RN  - 9647FM7Y3Z (Panobinostat)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - RUJ6Z9Y0DT (dactolisib)
MH  - Apoptosis/drug effects/genetics
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects/genetics
MH  - Cell Survival/drug effects/genetics
MH  - Drug Synergism
MH  - Glioblastoma/*metabolism
MH  - Histone Deacetylase Inhibitors/*pharmacology
MH  - Humans
MH  - Imidazoles/*pharmacology
MH  - Panobinostat/*pharmacology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Quinolines/*pharmacology
MH  - Signal Transduction/drug effects/genetics
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC6433629
OTO - NOTNLM
OT  - BEZ235
OT  - glioblastoma
OT  - panobinostat
COIS- No potential conflicts of interest were disclosed.
EDAT- 2019/04/10 06:00
MHDA- 2019/07/28 06:00
PMCR- 2019/02/01
CRDT- 2019/04/10 06:00
PHST- 2019/04/10 06:00 [entrez]
PHST- 2019/04/10 06:00 [pubmed]
PHST- 2019/07/28 06:00 [medline]
PHST- 2019/02/01 00:00 [pmc-release]
AID - 10.18999/nagjms.81.1.93 [doi]
PST - ppublish
SO  - Nagoya J Med Sci. 2019 Feb;81(1):93-102. doi: 10.18999/nagjms.81.1.93.