Inhibition of Gli leads to antitumor growth and enhancement of cisplatin-induced cytotoxicity in large cell neuroendocrine carcinoma of the lung

  • Authors:
    • Tsukasa Ishiwata
    • Shunichiro Iwasawa
    • Takahiro Ebata
    • Mengmeng Fan
    • Yuji Tada
    • Koichiro Tatsumi
    • Yuichi Takiguchi
  • View Affiliations

  • Published online on: January 3, 2018     https://doi.org/10.3892/or.2018.6183
  • Pages: 1148-1154
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Abstract

Large cell neuroendocrine carcinoma (LCNEC) of the lung is a highly aggressive tumor without established standard treatment. The Hedgehog (Hh) signal, which is critical in embryogenesis, is known to play important roles in maintaining a malignant phenotype in various cancers. The present study explored the possibility of targeting the Hh signal in the treatment of LCNEC by suppressing Hh downstream molecules, Smoothened (Smo) and GLI family zinc finger 1/2 (Gli1/2), in 3 human LCNEC cell lines. Smo inhibitor, BMS-833923, and Gli inhibitor, GANT61, downregulated Gli1 and 2, resulting in the suppression of the cell viability of the 3 cell lines as assessed using an MTT assay. The downregulation of Gli1 and/or Gli2 using siRNA for each gene also led to cell growth inhibition in the 3 cell lines. The downregulation of Gli1/2 made the cells more sensitive to cisplatin, resulting in increased apoptosis. These findings suggest that the Hh signaling pathway may be a candidate target for the treatment of LCNEC of the lung.
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March-2018
Volume 39 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Ishiwata T, Iwasawa S, Ebata T, Fan M, Tada Y, Tatsumi K and Takiguchi Y: Inhibition of Gli leads to antitumor growth and enhancement of cisplatin-induced cytotoxicity in large cell neuroendocrine carcinoma of the lung. Oncol Rep 39: 1148-1154, 2018
APA
Ishiwata, T., Iwasawa, S., Ebata, T., Fan, M., Tada, Y., Tatsumi, K., & Takiguchi, Y. (2018). Inhibition of Gli leads to antitumor growth and enhancement of cisplatin-induced cytotoxicity in large cell neuroendocrine carcinoma of the lung. Oncology Reports, 39, 1148-1154. https://doi.org/10.3892/or.2018.6183
MLA
Ishiwata, T., Iwasawa, S., Ebata, T., Fan, M., Tada, Y., Tatsumi, K., Takiguchi, Y."Inhibition of Gli leads to antitumor growth and enhancement of cisplatin-induced cytotoxicity in large cell neuroendocrine carcinoma of the lung". Oncology Reports 39.3 (2018): 1148-1154.
Chicago
Ishiwata, T., Iwasawa, S., Ebata, T., Fan, M., Tada, Y., Tatsumi, K., Takiguchi, Y."Inhibition of Gli leads to antitumor growth and enhancement of cisplatin-induced cytotoxicity in large cell neuroendocrine carcinoma of the lung". Oncology Reports 39, no. 3 (2018): 1148-1154. https://doi.org/10.3892/or.2018.6183