PMID- 27785067
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1178-6930 (Print)
IS  - 1178-6930 (Electronic)
IS  - 1178-6930 (Linking)
VI  - 9
DP  - 2016
TI  - Everolimus enhances cellular cytotoxicity of lapatinib via the eukaryotic 
      elongation factor-2 kinase pathway in nasopharyngeal carcinoma cells.
PG  - 6195-6201
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) has a high relapse and metastatic 
      rates; hence, development of new therapeutics is an immediate requirement. 
      Lapatinib and everolimus have been demonstrated to be effective in the treatment 
      of several carcinomas. This preclinical study aimed to investigate the effect and 
      mechanism of lapatinib combined with everolimus on NPC cells. METHODS: The Cell 
      Counting Kit 8 and colony formation assay were used to detect the effect of 
      lapatinib alone or lapatinib combined with everolimus on the growth and 
      proliferation of cells. Apoptosis was tested by flow cytometry and was further 
      confirmed by western blot. The targets of lapatinib and the effects of lapatinib 
      or everolimus on the eukaryotic elongation factor-2 (eEF-2) kinase pathway were 
      analyzed by western blot, which also evaluated autophagy activity. RESULTS: 
      Lapatinib inhibited the cellular viability and colony formation in NPC cells. At 
      24-72 h, the average half maximal inhibitory concentration (IC(50)) values of 
      lapatinib were ranging from 3 to 5 muM. This study further found that lapatinib 
      induced both apoptosis and autophagy in NPC cells, and this autophagic activity 
      was described as type II programmed cell death via an eEF-2 kinase-dependent 
      pathway. In addition, augmentation of lapatinib-induced autophagy by mammalian 
      target of rapamycin (mTOR) inhibitor everolimus enhanced the cytocidal effect of 
      lapatinib in NPC cells via the mTOR/S6 kinase/eEF-2 kinase pathway. CONCLUSION: 
      This study reveals that everolimus can sensitize NPC cells to lapatinib by the 
      activation of eEF-2 kinase and provides a potential model of combination therapy.
FAU - Liu, Lin
AU  - Liu L
AD  - Department of Medical Oncology.
FAU - Wang, Zhi-Hui
AU  - Wang ZH
AD  - Department of Medical Oncology.
FAU - Han, Jun
AU  - Han J
AD  - Department of Medical Oncology.
FAU - Tang, Con
AU  - Tang C
AD  - Department of Surgical Oncology, The Fifth Affiliated Hospital of Sun-Yat-Sen 
      University, Zhu Hai, Guangdong Province, People's Republic of China.
FAU - Chen, Nan
AU  - Chen N
AD  - Department of Medical Oncology.
FAU - Lin, Zhong
AU  - Lin Z
AD  - Department of Medical Oncology.
FAU - Peng, Pei-Jian
AU  - Peng PJ
AD  - Department of Medical Oncology.
LA  - eng
PT  - Journal Article
DEP - 20161011
PL  - New Zealand
TA  - Onco Targets Ther
JT  - OncoTargets and therapy
JID - 101514322
PMC - PMC5067011
OTO - NOTNLM
OT  - eEF-2K
OT  - everolimus
OT  - lapatinib
OT  - nasopharyngeal carcinoma
COIS- The authors report no conflicts of interest in this work.
EDAT- 2016/10/28 06:00
MHDA- 2016/10/28 06:01
PMCR- 2016/10/11
CRDT- 2016/10/28 06:00
PHST- 2016/10/28 06:00 [pubmed]
PHST- 2016/10/28 06:01 [medline]
PHST- 2016/10/28 06:00 [entrez]
PHST- 2016/10/11 00:00 [pmc-release]
AID - ott-9-6195 [pii]
AID - 10.2147/OTT.S115309 [doi]
PST - epublish
SO  - Onco Targets Ther. 2016 Oct 11;9:6195-6201. doi: 10.2147/OTT.S115309. eCollection 
      2016.