Effect of the STAT3 inhibitor STX-0119 on the proliferation of a temozolomide-resistant glioblastoma cell line

Int J Oncol. 2014 Jul;45(1):411-8. doi: 10.3892/ijo.2014.2439. Epub 2014 May 12.


Glioblastoma multiforme (GBM) is one of the most malignant and aggressive tumors and has a very poor prognosis, with a median survival time of less than 2 years. Once recurrence develops, there are few therapeutic approaches to control the growth of glioblastoma. In particular, temozolomide (TMZ)-resistant (TMZ-R) GBM is very difficult to treat, and a novel approach to overcome resistance is eagerly awaited. Previously, we reported a novel small molecule inhibitor of STAT3 dimerization, STX-0119, as a cancer therapeutic. In the current study, the efficacy of STX-0119 was evaluated against our established TMZ-resistant U87 cell line using quantitative PCR-based gene expression analysis, in vitro assay and animal experiments. The growth inhibitory effect of STX-0119 on U87 and TMZ-R U87 cells was moderate (IC₅₀, 34 and 45 µM, respectively). In particular, STX-0119 did not show significant inhibition of U87 tumor growth; however, it suppressed the growth of the TMZ-R U87 tumor in nude mice by more than 50%, and prolonged the median survival time compared to the control group. Quantitative PCR revealed that YKL-40, MAGEC1, MGMT, several EMT genes, mesenchymal genes and STAT3 target genes were upregulated, but most of those genes were downregulated by STX-0119 treatment. Furthermore, the invasive activity of TMZ-R U87 cells was significantly inhibited by STX-0119. YKL-40 levels in TMZ-R U87 cells and their supernatants were significantly decreased by STX-0119 administration. These results suggest that STX-0119 is an efficient therapeutic to overcome TMZ resistance in recurrent GBM tumors, and could be the next promising compound leading to survival prolongation, and YKL-40 may be a possible surrogate marker for STAT3 targeting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Dacarbazine / analogs & derivatives
  • Dacarbazine / pharmacology
  • Drug Resistance, Neoplasm / drug effects*
  • Epithelial-Mesenchymal Transition / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Glioblastoma / pathology*
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness / pathology*
  • Neoplasms, Experimental
  • Oxadiazoles / administration & dosage*
  • Oxadiazoles / pharmacology
  • Quinolines / administration & dosage*
  • Quinolines / pharmacology
  • STAT3 Transcription Factor / antagonists & inhibitors
  • STAT3 Transcription Factor / metabolism
  • Temozolomide
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • Oxadiazoles
  • Quinolines
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • STX-0119
  • Dacarbazine
  • Temozolomide