PMID- 27347100
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  - Gefitinib induces lung cancer cell autophagy and apoptosis via blockade of the 
      PI3K/AKT/mTOR pathway.
PG  - 63-68
AB  - Gefitinib is a selective inhibitor of the tyrosine kinase epidermal growth factor 
      receptor, which inhibits tumor pathogenesis, metastasis and angiogenesis, as well 
      as promoting apoptosis. Therefore, gefitinib presents an effective drug for the 
      targeted therapy of lung cancer. However, the underlying mechanisms by which 
      gefitinib induces lung cancer cell death remain unclear. To investigate the 
      effects of gefitinib on lung cancer cells and the mechanism of such, the present 
      study analyzed the effect of gefitinib on the autophagy, apoptosis and 
      proliferation of the A549 and A549-gefitinib-resistant (GR) cell lines GR. The 
      regulation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/ 
      mammalian target of rapamycin (mTOR) pathway was also investigated. Acridine 
      orange staining revealed that gefitinib induced autophagy of A549 cells but not 
      A549-GR cells. In addition, gefitinib promoted apoptosis and inhibited 
      proliferation of A549 cells but not A549-GR cells. Furthermore, western blot 
      analysis demonstrated that gefitinib treatment led to the downregulation of PI3K, 
      AKT, pAKT, mTOR and phosphorylated-mTOR protein expression in A549 cells but not 
      A549-GR cells. LY294002 blocked the PI3K/AKT/mTOR pathway and induced autophagy 
      and apoptosis of A549 cells, however, no synergistic effect was observed 
      following combined treatment with gefitinib and LY294002. In conclusion, the 
      results of the present study indicate that gefitinib promotes autophagy and 
      apoptosis of lung cancer cells via blockade of the PI3K/AKT/mTOR pathway, which 
      leads to lung cancer cell death.
FAU - Zhao, Zhong-Quan
AU  - Zhao ZQ
AD  - Department of Oncology, Fuzhou General Hospital, Fuzhou, Fujian 350025, P.R. 
      China.
FAU - Yu, Zhong-Yang
AU  - Yu ZY
AD  - Department of Oncology, Fuzhou General Hospital, Fuzhou, Fujian 350025, P.R. 
      China.
FAU - Li, Jie
AU  - Li J
AD  - Department of Oncology, Fuzhou General Hospital, Fuzhou, Fujian 350025, P.R. 
      China.
FAU - Ouyang, Xue-Nong
AU  - Ouyang XN
AD  - Department of Oncology, Fuzhou General Hospital, Fuzhou, Fujian 350025, P.R. 
      China.
LA  - eng
PT  - Journal Article
DEP - 20160518
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC4906680
OTO - NOTNLM
OT  - apoptosis
OT  - autophagy
OT  - gefitinib
OT  - lung cancer
OT  - mammalian target of rapamycin
OT  - phosphatidylinositol 3-kinase
OT  - protein kinase B
EDAT- 2016/06/28 06:00
MHDA- 2016/06/28 06:01
PMCR- 2016/05/18
CRDT- 2016/06/28 06:00
PHST- 2015/03/29 00:00 [received]
PHST- 2016/04/29 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- 2016/05/18 00:00 [pmc-release]
AID - OL-0-0-4606 [pii]
AID - 10.3892/ol.2016.4606 [doi]
PST - ppublish
SO  - Oncol Lett. 2016 Jul;12(1):63-68. doi: 10.3892/ol.2016.4606. Epub 2016 May 18.