PMID- 25872765
OWN - NLM
STAT- MEDLINE
DCOM- 20160316
LR  - 20220408
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 12
IP  - 2
DP  - 2015 Aug
TI  - PARP-1 promotes autophagy via the AMPK/mTOR pathway in CNE-2 human nasopharyngeal 
      carcinoma cells following ionizing radiation, while inhibition of autophagy 
      contributes to the radiation sensitization of CNE-2 cells.
PG  - 1868-76
LID - 10.3892/mmr.2015.3604 [doi]
AB  - It was previously reported that poly-(adenosine diphosphate-ribose) polymerase-1 
      (PARP-1) regulated ionizing radiation (IR)-induced autophagy in CNE-2 human 
      nasopharyngeal carcinoma cells. The present study aimed to investigate whether 
      PARP-1-mediated IR-induced autophagy occurred via activation of the liver kinase 
      B1 (LKB1)/adenosine monophosphate-activated protein kinase (AMPK)/mammalian 
      target of rapamycin (mTOR) signaling pathway in CNE-2 cells. In addition, the 
      effect of PARP-1 and AMPK inhibition on the radiation sensitization of CNE-2 
      cells was investigated. CNE-2 cells were treated with 10 Gy IR in the presence or 
      absence of the AMPK activator 
      5-amino-1-beta-D-ribofuranosyl-1H-imid-azole-4-carboxamide (AICAR). In addition, 
      IR-treated CNE-2 cells were transfected with lentivirus-delivered small-hairpin 
      RNA or treated with the AMPK inhibitor Compound C. Western blot analysis was used 
      to assess the protein expression of PARP-1, phosphorylated (p)-AMPK, 
      microtubule-associated protein 1 light chain 3 (LC3)-II and p-P70S6K. Cell 
      viability and clone formation assays were performed to determine the effect of 
      PARP-1 silencing and AMPK inhibition on the radiation sensitization of CNE-2 
      cells. The results showed that IR promoted PARP-1, p-AMPK and LC3-II protein 
      expression as well as decreased p-P70S6K expression compared with that of the 
      untreated cells. In addition, AICAR increased the expression of p-AMPK and LC3-II 
      as well as decreased p-P70S6K expression compared with that of the IR-only group; 
      however, AICAR did not increase PARP-1 expression. Furthermore, PARP-1 gene 
      silencing decreased the expression of PARP-1, p-AMPK and LC3-II as well as 
      increased p-P70S6K expression. Compound C decreased p-AMPK and LC3-Ⅱ expression 
      as well as increased p-P70S6K expression; however, Compound C did not increase 
      PARP-1 expression. Western blot analysis detected limited expression of p-LKB1 in 
      all treatment groups. Cell viability and clone formation assays revealed that 
      PARP-1 or AMPK inhibition reduced the proliferation of CNE-2 cells following IR. 
      In conclusion, the present study demonstrated that PARP-1 promoted autophagy via 
      the AMPK/mTOR pathway; in addition, PARP-1 or AMPK inhibition contributed to the 
      radiation sensitization of CNE-2 cells following IR. However, it remains to be 
      elucidated whether PARP-1 is an upstream mediator of the LKB1 pathway in CNE‑2 
      cells following IR.
FAU - Chen, Ze-Tan
AU  - Chen ZT
AD  - Department of Radiation Oncology, Affiliated Cancer Hospital of Guangxi Medical 
      University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, 
      Guangxi 530021, P.R. China.
FAU - Zhao, Wei
AU  - Zhao W
AD  - Department of Radiation Oncology, Affiliated Cancer Hospital of Guangxi Medical 
      University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, 
      Guangxi 530021, P.R. China.
FAU - Qu, Song
AU  - Qu S
AD  - Department of Radiation Oncology, Affiliated Cancer Hospital of Guangxi Medical 
      University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, 
      Guangxi 530021, P.R. China.
FAU - Li, Ling
AU  - Li L
AD  - Department of Radiation Oncology, Affiliated Cancer Hospital of Guangxi Medical 
      University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, 
      Guangxi 530021, P.R. China.
FAU - Lu, Xiao-Di
AU  - Lu XD
AD  - Department of Radiation Oncology, Affiliated Cancer Hospital of Guangxi Medical 
      University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, 
      Guangxi 530021, P.R. China.
FAU - Su, Fang
AU  - Su F
AD  - Department of Radiation Oncology, Affiliated Cancer Hospital of Guangxi Medical 
      University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, 
      Guangxi 530021, P.R. China.
FAU - Liang, Zhong-Guo
AU  - Liang ZG
AD  - Department of Radiation Oncology, Affiliated Cancer Hospital of Guangxi Medical 
      University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, 
      Guangxi 530021, P.R. China.
FAU - Guo, Si-Yan
AU  - Guo SY
AD  - Department of Radiation Oncology, Affiliated Cancer Hospital of Guangxi Medical 
      University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, 
      Guangxi 530021, P.R. China.
FAU - Zhu, Xiao-Dong
AU  - Zhu XD
AD  - Department of Radiation Oncology, Affiliated Cancer Hospital of Guangxi Medical 
      University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, 
      Guangxi 530021, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150409
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (MAP1LC3A protein, human)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Ribonucleotides)
RN  - 360-97-4 (Aminoimidazole Carboxamide)
RN  - EC 2.4.2.30 (PARP1 protein, human)
RN  - EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - F0X88YW0YK (AICA ribonucleotide)
SB  - IM
MH  - AMP-Activated Protein Kinases/antagonists & inhibitors/chemistry/*metabolism
MH  - Aminoimidazole Carboxamide/analogs & derivatives/pharmacology
MH  - Autophagy/drug effects/*radiation effects
MH  - Carcinoma
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects/radiation effects
MH  - Humans
MH  - Microscopy, Fluorescence
MH  - Microtubule-Associated Proteins/genetics/metabolism
MH  - Nasopharyngeal Carcinoma
MH  - Nasopharyngeal Neoplasms/metabolism/pathology
MH  - Phosphorylation/drug effects/radiation effects
MH  - Poly (ADP-Ribose) Polymerase-1
MH  - Poly(ADP-ribose) Polymerases/chemistry/genetics/*metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - *Radiation, Ionizing
MH  - Ribonucleotides/pharmacology
MH  - Ribosomal Protein S6 Kinases, 70-kDa/genetics/metabolism
MH  - Signal Transduction/drug effects/radiation effects
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC4463980
EDAT- 2015/04/16 06:00
MHDA- 2016/03/17 06:00
PMCR- 2015/04/09
CRDT- 2015/04/16 06:00
PHST- 2014/06/15 00:00 [received]
PHST- 2015/03/09 00:00 [accepted]
PHST- 2015/04/16 06:00 [entrez]
PHST- 2015/04/16 06:00 [pubmed]
PHST- 2016/03/17 06:00 [medline]
PHST- 2015/04/09 00:00 [pmc-release]
AID - mmr-12-02-1868 [pii]
AID - 10.3892/mmr.2015.3604 [doi]
PST - ppublish
SO  - Mol Med Rep. 2015 Aug;12(2):1868-76. doi: 10.3892/mmr.2015.3604. Epub 2015 Apr 9.