Rapamycin inhibited the function of lung CSCs via SOX2

Tumour Biol. 2016 Apr;37(4):4929-37. doi: 10.1007/s13277-015-4341-y. Epub 2015 Nov 3.

Abstract

The presence of cancer stem cells (CSCs) is the source of occurrence, aggravation, and recurrence of lung cancer. Accordingly, targeting killing the lung CSCs has been suggested to be an effective approach for lung cancer treatment. In this study, we showed that rapamycin inhibited the mammalian target of rapamycin (mTOR) signal transduction in A549 cells and improved the sensitivity to cisplatin (DDP). The mechanisms involve inhibition of the SOX2 expression, cell proliferation, epithelial-mesenchymal transition (EMT) phenotype, and sphere formation. Interestingly, knocked down SOX2 was a similar effect with rapamycin in A549 sphere. Furthermore, we showed that ectopic expression of Sox2 in A549 cells was sufficient to render them more resistant to rapamycin treatment in vitro. These data suggested that rapamycin inhibited the function of lung CSCs via SOX2. It will be of great interest to further explore the therapeutic strategies of lung cancer.

Keywords: Cancer stem cell; Lung cancer; Rapamycin; SOX2; mTOR.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / administration & dosage
  • Drug Resistance, Neoplasm / drug effects
  • Epithelial-Mesenchymal Transition / genetics
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / pathology
  • SOXB1 Transcription Factors / biosynthesis
  • SOXB1 Transcription Factors / genetics*
  • Sirolimus / administration & dosage*

Substances

  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Cisplatin
  • Sirolimus