Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang 110122, People's Republic of China.
Department of Pathology, College of Basic Medical Sciences and the First Affiliated Hospital, China Medical University, Shenyang 110122, People's Republic of China.
Cell Biol Int. 2018 Aug;42(8):994-1005. doi: 10.1002/cbin.10965. Epub 2018 May 29.
Lung cancer is one of life-threatening cancers in the worldwide. Liver kinase B1 (LKB1) has been reported to be closely related to cancers; however, the underlying mechanism of LKB1 in lung cancer remains unclear. In our study, a LKB1 specific shRNA was employed to down-regulate LKB1 levels and a LKB1 over-expression plasmid was constructed to up-regulate LKB1 levels. Thereafter, growth of lung cancer cells was assessed by MTT assay and flow cytometry. Effects of LKB1 on the activation of sonic hedgehog (Shh) signaling pathway were detected by Western blot. Effects of LKB1 on lung cancer growth and Shh signaling pathway activation were also assessed in vivo. Our results showed that LKB1 inhibited proliferation of lung cancer cells and induced their apoptosis. Moreover, LKB1 inhibited Shh signaling pathway activation. Our in vivo study also showed that LKB1 inhibited lung cancer growth in vivo and modulated Shh signaling pathway. Treatment with cyclopamine, a Shh signaling pathway inhibitor, reversed the effects of LKB1 silencing and enhanced the effects of LKB1 over-expression. Results of our study demonstrate that LKB1 inhibits lung cancer growth in vitro and in vivo through Shh signaling pathway.
肺癌是全球范围内危及生命的癌症之一。已有报道称肝激酶 B1（LKB1）与癌症密切相关，但 LKB1 在肺癌中的潜在机制尚不清楚。在我们的研究中，使用 LKB1 特异性 shRNA 下调 LKB1 水平，并构建 LKB1 过表达质粒上调 LKB1 水平。此后，通过 MTT assay 和流式细胞术评估肺癌细胞的生长。通过 Western blot 检测 LKB1 对 sonic hedgehog（Shh）信号通路激活的影响。还在体内评估了 LKB1 对肺癌生长和 Shh 信号通路激活的影响。我们的结果表明，LKB1 抑制肺癌细胞的增殖并诱导其凋亡。此外，LKB1 抑制 Shh 信号通路的激活。我们的体内研究还表明，LKB1 抑制体内肺癌的生长并调节 Shh 信号通路。用 Shh 信号通路抑制剂环巴胺处理可逆转 LKB1 沉默的作用，并增强 LKB1 过表达的作用。我们的研究结果表明，LKB1 通过 Shh 信号通路抑制体内外肺癌的生长。
