PMID- 21738008
OWN - NLM
STAT- MEDLINE
DCOM- 20120119
LR  - 20211203
IS  - 1555-8576 (Electronic)
IS  - 1538-4047 (Print)
IS  - 1538-4047 (Linking)
VI  - 12
IP  - 6
DP  - 2011 Sep 15
TI  - Augmentation of NVP-BEZ235's anticancer activity against human lung cancer cells 
      by blockage of autophagy.
PG  - 549-55
LID - 10.4161/cbt.12.6.16397 [doi]
AB  - Autophagy is a cellular lysosomal degradation pathway essential for regulation of 
      cell survival and death to maintain homeostasis. This process is negatively 
      regulated by mammalian target of rapamycin (mTOR) signaling and often counteracts 
      efficacy of certain cancer therapeutic agents. NVP-BEZ235 (BEZ235) is a novel, 
      orally bioavailable dual PI3K/mTOR inhibitor that has exhibited promising 
      activity against non-small cell lung cancer (NSCLC) in preclinical models. The 
      current study focuses on evaluating the role of BEZ235 in regulating autophagy. 
      BEZ235 was effective in inhibiting the growth of NSCLC cells including induction 
      of apoptosis. It also potently induced the expression of type-II LC3, indicating 
      induction of autophagy. When BEZ235 was used in combination with the lysosomal or 
      autophagic inhibitor chloroquine (CQ), enhanced inhibitory effects on monolayer 
      growth and colony formation of NSCLC cells was observed. In addition, enhanced 
      induction of apoptosis was also detected in cells exposed to the combination of 
      BEZ235 and CQ. Moreover, the combination of BEZ235 and CQ was more effective than 
      each single agent alone in inhibiting the growth of NSCLC xenografts in nude 
      mice. Thus, induction of autophagy by BEZ235 appears to be a survival mechanism 
      that may counteract its anticancer effects. Based on these, we suggest a strategy 
      to enhance BEZ235's anticancer efficacy by blockade of autophagy.
FAU - Xu, Cheng-Xiong
AU  - Xu CX
AD  - Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA, 
      USA.
FAU - Zhao, Liqun
AU  - Zhao L
FAU - Yue, Ping
AU  - Yue P
FAU - Fang, Guofu
AU  - Fang G
FAU - Tao, Hui
AU  - Tao H
FAU - Owonikoko, Taofeek K
AU  - Owonikoko TK
FAU - Ramalingam, Suresh S
AU  - Ramalingam SS
FAU - Khuri, Fadlo R
AU  - Khuri FR
FAU - Sun, Shi-Yong
AU  - Sun SY
LA  - eng
GR  - K23 CA164015/CA/NCI NIH HHS/United States
GR  - P01 CA116676/CA/NCI NIH HHS/United States
GR  - R01 CA118450/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110915
PL  - United States
TA  - Cancer Biol Ther
JT  - Cancer biology & therapy
JID - 101137842
RN  - 0 (Imidazoles)
RN  - 0 (Quinolines)
RN  - 886U3H6UFF (Chloroquine)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - RUJ6Z9Y0DT (dactolisib)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Autophagy/*drug effects
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Chloroquine/pharmacology/therapeutic use
MH  - Drug Synergism
MH  - Female
MH  - Humans
MH  - Imidazoles/*pharmacology/therapeutic use
MH  - Lung Neoplasms/*drug therapy/pathology
MH  - Mice
MH  - Mice, Nude
MH  - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/metabolism
MH  - Quinolines/*pharmacology/therapeutic use
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism
MH  - Tumor Burden/drug effects
MH  - Xenograft Model Antitumor Assays
PMC - PMC3218593
EDAT- 2011/07/09 06:00
MHDA- 2012/01/20 06:00
PMCR- 2012/09/15
CRDT- 2011/07/09 06:00
PHST- 2011/07/09 06:00 [entrez]
PHST- 2011/07/09 06:00 [pubmed]
PHST- 2012/01/20 06:00 [medline]
PHST- 2012/09/15 00:00 [pmc-release]
AID - 16397 [pii]
AID - 1538-4047-12-6-10 [pii]
AID - 10.4161/cbt.12.6.16397 [doi]
PST - ppublish
SO  - Cancer Biol Ther. 2011 Sep 15;12(6):549-55. doi: 10.4161/cbt.12.6.16397. Epub 
      2011 Sep 15.