DHFR and MDR1 upregulation is associated with chemoresistance in osteosarcoma stem-like cells

Yu Hsien Lee, Hui Wen Yang, Li Chiu Yang, Ming Yi Lu, Lo Lin Tsai, Shun Fa Yang, Yu Feng Huang, Ming Yung Chou, Cheng Chia Yu, Fang Wei Hu

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)


Tumor-initiating cells (TICs) are defined as a specialized subset of cells with tumor-initiating capacity that can initiate tumor growth, tumor relapse and metastasis. In the present study, osteosarcoma TICs (OS-TICs) were isolated and enriched from the osteosarcoma U2OS and MG-63 cell lines using sphere formation assays and serum-depleted media. These enriched OS-TICs showed the expression of several typical cancer stemness markers, including octamer-binding transcription factor 4, Nanog homeobox, cluster of differentiation (CD)117, Nestin and CD133, and the expression of ATP binding cassette subfamily G member 2, multidrug resistance protein 1 (MDR1) and dihydrofolate reductase (DHFR). Notably, in vitro and in vivo tumorigenic properties were enhanced in these OS-TICs. Additionally, methotrexate and doxorubicin are the most widely used anticancer agents against osteosarcoma, and the observed enhanced chemoresistance of OS-TICs to these two agents could be associated with the upregulation of DHFR and MDR1. These findings suggest that the upregulation of DHFR and MDR1 is associated with the development of chemoresistance of OS-TICs.

Original languageEnglish
Pages (from-to)171-179
Number of pages9
JournalOncology Letters
Issue number1
Publication statusPublished - 2017
Externally publishedYes


  • Chemo-resistance
  • Dihydrofolate reductase
  • Multidrug resistance protein 1
  • Tumor-initiating cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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