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Article

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 / Copyright

    Affiliations: Department of Respirology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan, Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan
  • Pages: 1148-1154
    |
    Published online on: January 3, 2018
       https://doi.org/10.3892/or.2018.6183
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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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Copy and paste a formatted citation
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
Copy and paste a formatted citation
x
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
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