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Article

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

  • Authors:
    • Tadashi Ashizawa
    • Yasuto Akiyama
    • Haruo Miyata
    • Akira Iizuka
    • Masaru Komiyama
    • Akiko Kume
    • Maho Omiya
    • Takashi Sugino
    • Akira Asai
    • Nakamasa Hayashi
    • Koichi Mitsuya
    • Yoko Nakasu
    • Ken Yamaguchi
  • View Affiliations / Copyright

    Affiliations: Immunotherapy Division, Shizuoka Cancer Center Research Institute, Sunto-gun, Shizuoka 411-8777, Japan, Division of Pathology, Shizuoka Cancer Center Hospital, Sunto-gun, Shizuoka 411-8777, Japan, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka 422-8526, Japan, Division of Neurosurgery, Shizuoka Cancer Center Hospital, Sunto-gun, Shizuoka 411-8777, Japan
  • Pages: 411-418
    |
    Published online on: May 12, 2014
       https://doi.org/10.3892/ijo.2014.2439
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Abstract

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.
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Copy and paste a formatted citation
Spandidos Publications style
Ashizawa T, Akiyama Y, Miyata H, Iizuka A, Komiyama M, Kume A, Omiya M, Sugino T, Asai A, Hayashi N, Hayashi N, et al: Effect of the STAT3 inhibitor STX-0119 on the proliferation of a temozolomide-resistant glioblastoma cell line. Int J Oncol 45: 411-418, 2014.
APA
Ashizawa, T., Akiyama, Y., Miyata, H., Iizuka, A., Komiyama, M., Kume, A. ... Yamaguchi, K. (2014). Effect of the STAT3 inhibitor STX-0119 on the proliferation of a temozolomide-resistant glioblastoma cell line. International Journal of Oncology, 45, 411-418. https://doi.org/10.3892/ijo.2014.2439
MLA
Ashizawa, T., Akiyama, Y., Miyata, H., Iizuka, A., Komiyama, M., Kume, A., Omiya, M., Sugino, T., Asai, A., Hayashi, N., Mitsuya, K., Nakasu, Y., Yamaguchi, K."Effect of the STAT3 inhibitor STX-0119 on the proliferation of a temozolomide-resistant glioblastoma cell line". International Journal of Oncology 45.1 (2014): 411-418.
Chicago
Ashizawa, T., Akiyama, Y., Miyata, H., Iizuka, A., Komiyama, M., Kume, A., Omiya, M., Sugino, T., Asai, A., Hayashi, N., Mitsuya, K., Nakasu, Y., Yamaguchi, K."Effect of the STAT3 inhibitor STX-0119 on the proliferation of a temozolomide-resistant glioblastoma cell line". International Journal of Oncology 45, no. 1 (2014): 411-418. https://doi.org/10.3892/ijo.2014.2439
Copy and paste a formatted citation
x
Spandidos Publications style
Ashizawa T, Akiyama Y, Miyata H, Iizuka A, Komiyama M, Kume A, Omiya M, Sugino T, Asai A, Hayashi N, Hayashi N, et al: Effect of the STAT3 inhibitor STX-0119 on the proliferation of a temozolomide-resistant glioblastoma cell line. Int J Oncol 45: 411-418, 2014.
APA
Ashizawa, T., Akiyama, Y., Miyata, H., Iizuka, A., Komiyama, M., Kume, A. ... Yamaguchi, K. (2014). Effect of the STAT3 inhibitor STX-0119 on the proliferation of a temozolomide-resistant glioblastoma cell line. International Journal of Oncology, 45, 411-418. https://doi.org/10.3892/ijo.2014.2439
MLA
Ashizawa, T., Akiyama, Y., Miyata, H., Iizuka, A., Komiyama, M., Kume, A., Omiya, M., Sugino, T., Asai, A., Hayashi, N., Mitsuya, K., Nakasu, Y., Yamaguchi, K."Effect of the STAT3 inhibitor STX-0119 on the proliferation of a temozolomide-resistant glioblastoma cell line". International Journal of Oncology 45.1 (2014): 411-418.
Chicago
Ashizawa, T., Akiyama, Y., Miyata, H., Iizuka, A., Komiyama, M., Kume, A., Omiya, M., Sugino, T., Asai, A., Hayashi, N., Mitsuya, K., Nakasu, Y., Yamaguchi, K."Effect of the STAT3 inhibitor STX-0119 on the proliferation of a temozolomide-resistant glioblastoma cell line". International Journal of Oncology 45, no. 1 (2014): 411-418. https://doi.org/10.3892/ijo.2014.2439
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