title: [Activation of mTOR signaling pathway in cancer stem cells of nasopharyngeal carcinoma and inhibitive effect of rapamycin against the cancer stem cells].
abstract: OBJECTIVE
  To study the mTOR expression of cancer stem cells(CSCs) in nasopharyngeal carcinoma and preliminarily explore the mechanism of inhibiting its proliferation with rapamycin.
  
  
  METHODS
  Nasopharyngeal carcinoma spherical cells were gathered by using serum-free suspension culture method, CCK8 assay was used to detect cell proliferation, Western blot assay was used to detect the expression of CD44, OCT4, SOX2 and mTOR signaling. The spherical cells and CNE2 were treated with rapamycin in concentrations of 0, 0.1, 1.0, 10.0, 100.0, 1000.0 nmol/L, CCK8 assay was used to detect cell inhibition ratio, Western blot assay was used to detect the expression of mTOR signaling of nasopharyngeal carcinoma spherical cells.
  
  
  RESULTS
  Compared with CNE2, the spherical cells exhibited a high proliferation rate in RPMI 1640 medium supplemented with fetal bovine serum, and overexpressed in OCT4, SOX2 (P < 0.05), but not that of CD44 (P > 0.05). Although the expression levels of mTOR, P70S6, 4EBP1 were not significantly different between the two kinds of cells (P > 0.05) the proteins of phosphorylation activation form of them (P-mTOR, P-P70S6, P-4EBP1) were highly expressed in spherical cells (P < 0.05). The spherical cells and CNE2 were treated with rapamycin in different concentrations, the concentrations for 50% of maximal effect of spherical cells and CNE2 were 2.59 nmol/L and 78.12 nmol/L respectively, rapamycin inhibited the spherical cells more strongly compared with CNEZ. The expression levels of P-mTOR, P-70S6, P-4EBP1 in spherical cells were gradually decreased with increasing of the concentrations of rapamycin, but the difference of the expression levels of mTOR, P70S6, 4EBP1 were not significant.
  
  
  CONCLUSIONS
  The proteins of mTOR signaling pathway of CSCs in nasopharyngeal carcinoma are overexpressed, and rapamycin can effectively inhibit cell proliferation of CSCs in nasopharyngeal carcinoma by blocking mTOR signaling pathway.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Renyu
authors.initials: R
authors.lastname: Lin
authors.forename: Ziheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Chunguang
authors.initials: C
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D002277:Carcinoma; D018797:Cell Cycle Proteins; D049109:Cell Proliferation; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus