PMID- 26202311
OWN - NLM
STAT- MEDLINE
DCOM- 20160517
LR  - 20211203
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Print)
IS  - 1019-6439 (Linking)
VI  - 47
IP  - 3
DP  - 2015 Sep
TI  - Downregulation of cancer stem cell properties via mTOR signaling pathway 
      inhibition by rapamycin in nasopharyngeal carcinoma.
PG  - 909-17
LID - 10.3892/ijo.2015.3100 [doi]
AB  - Rapamycin, a mammalian target of rapamycin (mTOR) signaling inhibitor, inhibits 
      cancer cell proliferation and tumor formation, including in nasopharyngeal 
      carcinoma (NPC), which we proved in a previous study. However, whether rapamycin 
      affects cancer stem cells (CSCs) is unclear. In examining samples of NPCs, we 
      found regions of CD44-positive cancer cells co-expressing the stem cell biomarker 
      OCT4, suggesting the presence of CSCs. Following this, we used double-label 
      immunohistochemistry to identify whether the mTOR signaling pathway was activated 
      in CD44-positive CSCs in NPCs. We used a CCK-8 assay and western blotting to 
      explore whether the stem cell biomarkers CD44 and SOX2 and the invasion protein 
      MMP-2 could be suppressed by treatment with rapamycin in cultured primary NPC 
      cells and secondary tumors in BALB/c nude mice. Interestingly, we found that 
      rapamycin inhibited mTOR signaling in addition to simultaneously downregulating 
      the expression of CD44, SOX2 and MMP-2 and that it affected cell growth and tumor 
      size and weight both in vitro and in vivo. Collectively, we confirmed for the 
      first time that CSC properties are reduced and invasion potential is restrained 
      in response to mTOR signaling inhibition in NPC. This evidence indicates that the 
      targeted inhibition of CSC properties may provide a novel strategy to treat 
      cancer.
FAU - Yang, Chunguang
AU  - Yang C
AD  - Department of Otolaryngology, Head and Neck Surgery, Xiang Ya Hospital, Central 
      South University, Changsha, Hunan, P.R. China.
FAU - Zhang, Yue
AU  - Zhang Y
AD  - Department of Otolaryngology, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang, P.R. China.
FAU - Zhang, Yu
AU  - Zhang Y
AD  - Department of Otolaryngology, Dong Feng Hospital, Hubei University of Medicine, 
      Shiyan, Hubei, P.R. China.
FAU - Zhang, Ziheng
AU  - Zhang Z
AD  - Department of Otolaryngology, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang, P.R. China.
FAU - Peng, Jianhua
AU  - Peng J
AD  - Department of Otolaryngology, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang, P.R. China.
FAU - Li, Zhi
AU  - Li Z
AD  - Department of Otolaryngology, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang, P.R. China.
FAU - Han, Liang
AU  - Han L
AD  - Department of Otolaryngology, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang, P.R. China.
FAU - You, Quanjie
AU  - You Q
AD  - Department of Otolaryngology, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang, P.R. China.
FAU - Chen, Xiaoyu
AU  - Chen X
AD  - Department of Otolaryngology, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang, P.R. China.
FAU - Rao, Xingwang
AU  - Rao X
AD  - Department of Otolaryngology, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang, P.R. China.
FAU - Zhu, Yi
AU  - Zhu Y
AD  - Department of Otolaryngology, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang, P.R. China.
FAU - Liao, Zhisu
AU  - Liao Z
AD  - Department of Otolaryngology, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150721
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Antibiotics, Antineoplastic/*administration & dosage/pharmacology
MH  - Biomarkers, Tumor/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Mice
MH  - Nasopharyngeal Neoplasms/*drug therapy/metabolism
MH  - Neoplastic Stem Cells/*drug effects/metabolism
MH  - Signal Transduction/drug effects
MH  - Sirolimus/*administration & dosage/pharmacology
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Xenograft Model Antitumor Assays
PMC - PMC4532219
EDAT- 2015/07/24 06:00
MHDA- 2016/05/18 06:00
PMCR- 2015/07/21
CRDT- 2015/07/24 06:00
PHST- 2015/04/25 00:00 [received]
PHST- 2015/07/03 00:00 [accepted]
PHST- 2015/07/24 06:00 [entrez]
PHST- 2015/07/24 06:00 [pubmed]
PHST- 2016/05/18 06:00 [medline]
PHST- 2015/07/21 00:00 [pmc-release]
AID - ijo-47-03-0909 [pii]
AID - 10.3892/ijo.2015.3100 [doi]
PST - ppublish
SO  - Int J Oncol. 2015 Sep;47(3):909-17. doi: 10.3892/ijo.2015.3100. Epub 2015 Jul 21.