PMID- 27347108
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1792-1074 (Print)
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Linking)
VI  - 12
IP  - 1
DP  - 2016 Jul
TI  - Autophagy inhibition enhances colorectal cancer apoptosis induced by dual 
      phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235.
PG  - 102-106
AB  - Phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) 
      signaling pathway performs a central role in tumorigenesis and is constitutively 
      activated in many malignancies. As a novel dual PI3K/mTOR inhibitor currently 
      undergoing evaluation in a phase I/II clinical trial, NVP-BEZ235 indicates a 
      significant antitumor efficacy in diverse solid tumors, including colorectal 
      cancer (CRC). Autophagy is a catabolic process that maintains cellular 
      homeostasis and reduces diverse stresses through lysosomal recycling of the 
      unnecessary and damaged cell components. This process is also observed to 
      antagonize the antitumor efficacy of PI3K/mTOR inhibitor agents such as 
      NVP-BEZ235, via apoptosis inhibition. In the present study, we investigated 
      anti-proliferative and apoptosis-inducing ability of NVP-BEZ235 in SW480 cells 
      and the crosstalk between autophagy and apoptosis in SW480 cells treated with 
      NVP-BEZ235 in combination with an autophagy inhibitor. The results revealed that, 
      NVP-BEZ235 effectively inhibit the growth of SW480 cells by targeting the 
      PI3K/mTOR signaling pathway and induced apoptosis. The inhibition of autophagy 
      with 3-methyladenine or chloroquine inhibitors in combination with NVP-BEZ235 in 
      SW480 cells enhanced the apoptotic rate as componets to NVP-BEZ235 alone. In 
      conclusion, the findings provide a rationale for chemotherapy targeting the 
      PI3K/mTOR signaling pathway presenting a potential therapeutic strategy to 
      enhance the efficacy of dual PI3K/mTOR inhibitor NVP-BEZ235 in combination with 
      an autophagy inhibitor in CRC treatment and treatment of other tumors.
FAU - Yang, Xiaoyu
AU  - Yang X
AD  - Department of Pathology, Xinxiang Medical University, Xinxiang, Henan 453003, 
      P.R. China.
FAU - Niu, Bingxuan
AU  - Niu B
AD  - College of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. 
      China.
FAU - Wang, Libo
AU  - Wang L
AD  - Department of Gastroenterology, The First Affiliated Hospital of Jilin 
      University, Changchun, Jilin 130021, P.R. China.
FAU - Chen, Meiling
AU  - Chen M
AD  - Department of Oncology, The First Affiliated Hospital of Xinxiang Medical 
      University, Xinxiang, Henan 453100, P.R. China.
FAU - Kang, Xiaochun
AU  - Kang X
AD  - Department of Oncology, The First Affiliated Hospital of Xinxiang Medical 
      University, Xinxiang, Henan 453100, P.R. China.
FAU - Wang, Luonan
AU  - Wang L
AD  - Department of Oncology, The First Affiliated Hospital of Xinxiang Medical 
      University, Xinxiang, Henan 453100, P.R. China.
FAU - Ji, Yinghua
AU  - Ji Y
AD  - Department of Oncology, The First Affiliated Hospital of Xinxiang Medical 
      University, Xinxiang, Henan 453100, P.R. China.
FAU - Zhong, Jiateng
AU  - Zhong J
AD  - Department of Pathology, Xinxiang Medical University, Xinxiang, Henan 453003, 
      P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20160517
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC4906634
OTO - NOTNLM
OT  - NVP-BEZ235
OT  - apoptosis
OT  - autophagy
OT  - colorectal cancer
OT  - phosphatidylinositol 3-kinase/mammalian target of rapamycin
EDAT- 2016/06/28 06:00
MHDA- 2016/06/28 06:01
PMCR- 2016/05/17
CRDT- 2016/06/28 06:00
PHST- 2015/12/01 00:00 [received]
PHST- 2016/05/17 00:00 [accepted]
PHST- 2016/06/28 06:00 [entrez]
PHST- 2016/06/28 06:00 [pubmed]
PHST- 2016/06/28 06:01 [medline]
PHST- 2016/05/17 00:00 [pmc-release]
AID - OL-0-0-4590 [pii]
AID - 10.3892/ol.2016.4590 [doi]
PST - ppublish
SO  - Oncol Lett. 2016 Jul;12(1):102-106. doi: 10.3892/ol.2016.4590. Epub 2016 May 17.