Yan Bing, Zhao Dejian, Yao Yinan, Bao Zhang, Lu Guohua, Zhou Jianying
1. Department of Respiratory Diseases, First Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
2. Department of Clinical Laboratory, First Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.
Int J Biol Sci. 2016 May 25;12(7):850-60. doi: 10.7150/ijbs.14773. eCollection 2016.
Lung cancer is the leading cause of cancer mortality around the world. Despite advances in the targeted therapy, patients with lung squamous cell carcinoma(SCC) still benefit few from it, and the search for potential effective therapies is imperative. Here, we demonstrated that deguelin induced significant apoptosis of lung SCC cells in vitro. Importantly, we found deguelin down-regulated the expression of galectin-1, which was involved in a wide range of tumorous physiologic process. Thus, we both over-expressed and down-regulated galectin-1 to perform its role in deguelin-induced apoptosis. We found that increased galectin-1 attenuated apoptosis of SCC cells exposed to deguelin, while galectin-1 knockdown sensitized lung cancer cells to deguelin treatment. Additionally, we observed that down-regulation of galectin-1 resulted in suppression of Ras/Raf/ERK pathway which was involved in deguelin-induced cell apoptosis. We also found that deguelin had a significant anti-tumor ability with decline of galectin-1 in vivo. In conclusion, these findings confirm that deguelin may act as a new chemo-preventive agent through inducing apoptosis of lung SCC cells in a galectin-1 dependent manner.
肺癌是全球癌症死亡的主要原因。尽管靶向治疗取得了进展，但肺鳞状细胞癌（SCC）患者从中获益仍然很少，因此寻找潜在的有效治疗方法势在必行。在此，我们证明了鱼藤素在体外可诱导肺SCC细胞发生显著凋亡。重要的是，我们发现鱼藤素可下调半乳糖凝集素-1的表达，而半乳糖凝集素-1参与了广泛的肿瘤生理过程。因此，我们通过过表达和下调半乳糖凝集素-1来研究其在鱼藤素诱导凋亡中的作用。我们发现，增加半乳糖凝集素-1可减弱鱼藤素诱导的SCC细胞凋亡，而敲低半乳糖凝集素-1可使肺癌细胞对鱼藤素治疗更敏感。此外，我们观察到下调半乳糖凝集素-1会导致Ras/Raf/ERK信号通路受到抑制，而该信号通路参与了鱼藤素诱导的细胞凋亡。我们还发现，在体内，随着半乳糖凝集素-1的减少，鱼藤素具有显著的抗肿瘤能力。总之，这些发现证实鱼藤素可能通过以半乳糖凝集素-1依赖的方式诱导肺SCC细胞凋亡而作为一种新的化学预防剂。
