PMID- 31613929
OWN - NLM
STAT- MEDLINE
DCOM- 20200316
LR  - 20211204
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 14
IP  - 10
DP  - 2019
TI  - Celecoxib enhances the sensitivity of non-small-cell lung cancer cells to 
      radiation-induced apoptosis through downregulation of the Akt/mTOR signaling 
      pathway and COX-2 expression.
PG  - e0223760
LID - 10.1371/journal.pone.0223760 [doi]
LID - e0223760
AB  - The current study aimed to identify the radiosensitizing effect of celecoxib, a 
      selective cyclooxygenase-2 (COX-2) inhibitor, in combination with radiotherapy in 
      non-small-cell lung cancer (NSCLC) cells. The combination of celecoxib 
      potentiated radiation-induced apoptosis; however, no changes in cell cycle 
      distribution and number of phosphorylated histone H2AX foci were detected, 
      indicating a DNA damage-independent mechanism. In an in vivo mouse model, the 
      tumor size was significantly decreased in the group combining celecoxib with 
      radiation compared with the radiation only group. Phosphorylation of protein 
      kinase B (Akt) and mammalian target of rapamycin (mTOR), as well as expression of 
      COX-2 were significantly downregulated in cells treated with the combination of 
      celecoxib and radiation compared with the radiation only group. The result 
      indicated that celecoxib exhibits radiosensitizing effects through COX-2 and 
      Akt/mTOR-dependent mechanisms. Induction the Akt/mTOR signaling pathway promotes 
      radioresistance in various cancers, including NSCLC. Therefore, the current study 
      suggested the therapeutic potential of combination therapy of celecoxib and 
      radiation in the prevention of radioresistance.
FAU - Zhang, Pan
AU  - Zhang P
AD  - Key Laboratory of Luminescence and Real-Time Analytical Chemistry, Ministry of 
      Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 
      P. R. China.
FAU - He, Dan
AU  - He D
AD  - Department of Oncology, Nuclear Industry Hospital, Chengdu, Sichuan, P. R. China.
FAU - Song, Erqun
AU  - Song E
AD  - Key Laboratory of Luminescence and Real-Time Analytical Chemistry, Ministry of 
      Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 
      P. R. China.
FAU - Jiang, Mingdong
AU  - Jiang M
AD  - Department of Radiation Oncology, The Ninth People's Hospital of Chongqing, 
      Chongqing, P. R. China.
FAU - Song, Yang
AU  - Song Y
AUID- ORCID: 0000-0001-7716-9216
AD  - Key Laboratory of Luminescence and Real-Time Analytical Chemistry, Ministry of 
      Education, College of Pharmaceutical Sciences, Southwest University, Chongqing, 
      P. R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191015
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Radiation-Sensitizing Agents)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
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  - JCX84Q7J1L (Celecoxib)
SB  - IM
EIN - PLoS One. 2019 Oct 30;14(10):e0224843. PMID: 31665187
MH  - A549 Cells
MH  - Animals
MH  - Carcinoma, Non-Small-Cell Lung/metabolism/*therapy
MH  - Celecoxib/*administration & dosage/pharmacology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects/radiation effects
MH  - Cell Survival/drug effects/radiation effects
MH  - Cyclooxygenase 2/*metabolism
MH  - Gene Expression Regulation, Neoplastic/drug effects/radiation effects
MH  - Humans
MH  - Lung Neoplasms/metabolism/*therapy
MH  - Male
MH  - Mice
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Radiation-Sensitizing Agents/*administration & dosage/pharmacology
MH  - Signal Transduction/drug effects/radiation effects
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Xenograft Model Antitumor Assays
PMC - PMC6793859
COIS- The authors have declared that no competing interests exist.
EDAT- 2019/10/16 06:00
MHDA- 2020/03/17 06:00
PMCR- 2019/10/15
CRDT- 2019/10/16 06:00
PHST- 2019/04/01 00:00 [received]
PHST- 2019/09/27 00:00 [accepted]
PHST- 2019/10/16 06:00 [entrez]
PHST- 2019/10/16 06:00 [pubmed]
PHST- 2020/03/17 06:00 [medline]
PHST- 2019/10/15 00:00 [pmc-release]
AID - PONE-D-19-09229 [pii]
AID - 10.1371/journal.pone.0223760 [doi]
PST - epublish
SO  - PLoS One. 2019 Oct 15;14(10):e0223760. doi: 10.1371/journal.pone.0223760. 
      eCollection 2019.