PMID- 28000883
OWN - NLM
STAT- MEDLINE
DCOM- 20170404
LR  - 20220317
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 37
IP  - 2
DP  - 2017 Feb
TI  - 2-Methoxyestradiol inhibits the proliferation and migration and reduces the 
      radioresistance of nasopharyngeal carcinoma CNE-2 stem cells via NF-kappaB/HIF-1 
      signaling pathway inactivation and EMT reversal.
PG  - 793-802
LID - 10.3892/or.2016.5319 [doi]
AB  - Accumulating evidence indicates that cancer stem cells (CSCs) are a source of 
      resistance to radiation therapy (RT); however, the mechanism of this resistance 
      remains unclear. 2-Methoxyestradiol (2-ME2) is a metabolic product of estrogen in 
      the body. Recent studies have found that 2-ME2 regulates the activation of 
      transcription factors, including nuclear factor (NF)-kappaB/hypoxia-inducible 
      factor-1 (HIF-1), thus contributing to tumor cell apoptosis and chemosensitivity. 
      Therefore, 2-ME2 is being studied as a potential anticancer drug. The purpose of 
      this study was to determine the effect and mechanism by which 2-ME2 inhibits 
      nasopharyngeal carcinoma CNE-2 stem-like cell (NPCSC) proliferation and migration 
      and reduces NPCSC radioresistance. This study has important significance for 
      reducing the radioresistance of these cells to improve the cure rate of NPC. 
      First, the NPCSCs were collected in a serum-free culture system and then 
      identified by relevant experiments. The NPCSCs were treated with 2-ME2 (0-8 microM) 
      combined with X-ray exposure and Cell Counting Kit-8 (CCK-8), Transwell assay, 
      colony formation assay, western blot analysis, RT-PCR, flow cytometry and RNA 
      interference technology were used to explore the effect and mechanism of 2-ME2 on 
      NPCSCs. The results showed that the microspheres collected in the serum‑free 
      culture system possessed CSC traits and radioresistance. 2-ME2 obviously 
      inhibited NPCSC growth and migration and reduced NPCSC radioresistance. 2-ME2 
      decreased NF-kappaB p65 and HIF-1alpha protein expression, downregulated NF-kappaB p65 
      nuclear localization, and reversed epithelial-mesenchymal transition (EMT). NF-kappaB 
      p65 knockdown reduced HIF-1alpha expression, reversed EMT, and enhanced the 
      suppressive effect of 2-ME2 on NPCSCs. Collectively, these data indicate that 
      2-ME2 inhibits NPCSC proliferation and migration and reduces the radioresistance 
      of NPCSCs via NF-kappaB/HIF-1 signaling pathway inactivation and EMT reversal.
FAU - Wu, Shun-Long
AU  - Wu SL
AD  - Department of Oncology, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing 400016, P.R. China.
FAU - Li, Ya-Jun
AU  - Li YJ
AD  - Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
FAU - Liao, Kui
AU  - Liao K
AD  - Department of Oncology, The First Affiliated Hospital of Chongqing Medical 
      University, Chongqing 400016, P.R. China.
FAU - Shi, Lei
AU  - Shi L
AD  - Department of Oncology, Affiliated Hospital of Zunyi Medical College, Zunyi, 
      Guizhou 563000, P.R. China.
FAU - Zhang, Na
AU  - Zhang N
AD  - Department of Oncology and Radiation Medicine, College of Basic Medicine, 
      Chongqing Medical University, Chongqing 400016, P.R. China.
FAU - Liu, Shuang
AU  - Liu S
AD  - Department of Oncology and Radiation Medicine, College of Basic Medicine, 
      Chongqing Medical University, Chongqing 400016, P.R. China.
FAU - Hu, Yao-Yao
AU  - Hu YY
AD  - Department of Oncology, Affiliated Hospital of Zunyi Medical College, Zunyi, 
      Guizhou 563000, P.R. China.
FAU - Li, Shao-Lin
AU  - Li SL
AD  - Department of Oncology and Radiation Medicine, College of Basic Medicine, 
      Chongqing Medical University, Chongqing 400016, P.R. China.
FAU - Wang, Ying
AU  - Wang Y
AD  - Department of Radiotherapy, Chongqing Cancer Institute, Chongqing 400030, 
      P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20161214
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tubulin Modulators)
RN  - 4TI98Z838E (Estradiol)
RN  - 6I2QW73SR5 (2-Methoxyestradiol)
SB  - IM
MH  - 2-Methoxyestradiol
MH  - Apoptosis/drug effects/radiation effects
MH  - Blotting, Western
MH  - Cell Differentiation/drug effects/radiation effects
MH  - Cell Movement/drug effects/radiation effects
MH  - Cell Proliferation/drug effects/radiation effects
MH  - Down-Regulation
MH  - Epithelial-Mesenchymal Transition/*drug effects/radiation effects
MH  - Estradiol/*analogs & derivatives/pharmacology
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*antagonists & 
      inhibitors/genetics/metabolism
MH  - NF-kappa B/*antagonists & inhibitors/genetics/metabolism
MH  - Nasopharyngeal Neoplasms/drug therapy/metabolism/*pathology/radiotherapy
MH  - Neoplastic Stem Cells/*drug effects/metabolism/radiation effects
MH  - RNA, Messenger/genetics
MH  - Radiation Tolerance/*drug effects
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/drug effects/radiation effects
MH  - Tubulin Modulators/pharmacology
MH  - Tumor Cells, Cultured
EDAT- 2016/12/22 06:00
MHDA- 2017/04/05 06:00
CRDT- 2016/12/22 06:00
PHST- 2016/04/17 00:00 [received]
PHST- 2016/05/31 00:00 [accepted]
PHST- 2016/12/22 06:00 [pubmed]
PHST- 2017/04/05 06:00 [medline]
PHST- 2016/12/22 06:00 [entrez]
AID - 10.3892/or.2016.5319 [doi]
PST - ppublish
SO  - Oncol Rep. 2017 Feb;37(2):793-802. doi: 10.3892/or.2016.5319. Epub 2016 Dec 14.