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.
Oncol Rep. 2018 Mar;39(3):1148-1154. doi: 10.3892/or.2018.6183. Epub 2018 Jan 3.
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.
肺大细胞神经内分泌癌（LCNEC）是一种侵袭性很强的肿瘤，目前尚无标准治疗方法。Hedgehog（Hh）信号通路在胚胎发生中起关键作用，已知在多种癌症中维持恶性表型方面发挥着重要作用。本研究通过抑制 Hh 下游分子 Smoothened（Smo）和 GLI 家族锌指蛋白 1/2（Gli1/2），探讨了针对 LCNEC 中 Hh 信号通路的治疗可能性，该研究在 3 个人类 LCNEC 细胞系中进行。Smo 抑制剂 BMS-833923 和 Gli 抑制剂 GANT61 下调 Gli1 和 Gli2，MTT 检测结果显示，这导致 3 种细胞系的细胞活力受到抑制。用每种基因的 siRNA 下调 Gli1 和/或 Gli2 也导致 3 种细胞系的细胞生长受到抑制。下调 Gli1/2 使细胞对顺铂更敏感，导致细胞凋亡增加。这些发现表明，Hh 信号通路可能是治疗肺大细胞神经内分泌癌的候选靶点。
