Department of Respiratory Medicine, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Department of Respiratory Rehabilitation, Shanghai Fourth Rehabilitation Hospital, Shanghai, China.
J Int Med Res. 2021 May;49(5):3000605211016562. doi: 10.1177/03000605211016562.
Small-cell lung cancer (SCLC) accounts for approximately 15% to 20% of all lung cancers, and it is the leading cause of tumor-related deaths globally. This study explored the molecular mechanisms underlying the development of SCLC.
The correlations of phosphoinositide-dependent kinase-1 (PDPK1), p-Akt, and Hedgehog expression with patient characteristics were analyzed using SCLC specimens, and their expression was measured in BEAS-2B cells (control) and the SCLC cell lines H82, H69, H446, H146, and H526. Transfection experiments were performed to inhibit or activate gene expression in cells. We then measured the proliferation and migration of H146 cells.
PDPK1, p-Akt, and Hedgehog expression was significantly higher in SCLC tissues, and their expression was correlated with patient characteristics. p-Akt expression was significantly correlated with Hedgehog expression. In H146 cells, PDPK1 and p-Akt were significantly upregulated. Silencing of PDPK1 or Akt and inhibition of Hedgehog significantly inhibited the proliferation and migration of H146 cells. PDPK1 and Akt affected Hedgehog expression, but Hedgehog did not affect PDPK1 or p-Akt expression.
The interaction between the PDPK1-Akt pathway and the Hedgehog pathway influences the prognosis, growth, and migration of SCLC.
小细胞肺癌（SCLC）约占所有肺癌的 15%至 20%，是全球肿瘤相关死亡的主要原因。本研究探讨了 SCLC 发生的分子机制。
使用 SCLC 标本分析磷酸肌醇依赖性激酶-1（PDPK1）、p-Akt 和 Hedgehog 表达与患者特征的相关性，并在 BEAS-2B 细胞（对照）和 SCLC 细胞系 H82、H69、H446、H146 和 H526 中测量其表达。通过转染实验抑制或激活细胞中的基因表达。然后测量 H146 细胞的增殖和迁移。
PDPK1、p-Akt 和 Hedgehog 表达在 SCLC 组织中明显升高，其表达与患者特征相关。p-Akt 表达与 Hedgehog 表达明显相关。在 H146 细胞中，PDPK1 和 p-Akt 明显上调。沉默 PDPK1 或 Akt 并抑制 Hedgehog 显著抑制 H146 细胞的增殖和迁移。PDPK1 和 Akt 影响 Hedgehog 表达，但 Hedgehog 不影响 PDPK1 或 p-Akt 表达。
PDPK1-Akt 通路和 Hedgehog 通路之间的相互作用影响 SCLC 的预后、生长和迁移。
