Lin Yingying, Xie Guobin, Xia Ji, Su Dan, Liu Jie, Jiang Fuquan, Xu Yang
School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China.
School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, PR China.
Biochim Biophys Acta. 2016 Feb;1864(2):204-10. doi: 10.1016/j.bbapap.2015.11.001. Epub 2015 Nov 11.
Tubeimoside-1 (TBMS1) exerts its anticancer effects by inducing G2/M arrest and apoptosis of cancer cells. However, the precise molecular mechanism of its anti-tumor effects has not been fully elucidated, especially the signaling pathways involved in the early stage of TBMS1 stimulation. In this study, we employed stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics approach and identified 439 proteins that exhibit significant differential expressions in NCI-H460 lung cancer cells upon exposure to TBMS1. Gene ontology and network analysis using DAVID and STRING on-line tools revealed that several nucleolar stress (ribosomal biogenesis) response proteins were differentially regulated by TBMS1. Functional validation demonstrated that TBMS1-induced NCI-H460 cell cytotoxicity involved nucleolar stress-induced p53/murine double minute clone 2 (MDM2), mTOR, and NF-κB signaling pathways.
土贝母苷甲（TBMS1）通过诱导癌细胞的G2/M期阻滞和凋亡发挥其抗癌作用。然而，其抗肿瘤作用的确切分子机制尚未完全阐明，尤其是TBMS1刺激早期所涉及的信号通路。在本研究中，我们采用基于细胞培养中氨基酸稳定同位素标记（SILAC）的定量蛋白质组学方法，鉴定出439种在暴露于TBMS1的NCI-H460肺癌细胞中表现出显著差异表达的蛋白质。使用DAVID和STRING在线工具进行的基因本体论和网络分析表明，几种核仁应激（核糖体生物合成）反应蛋白受TBMS1的差异调节。功能验证表明，TBMS1诱导的NCI-H460细胞毒性涉及核仁应激诱导的p53/小鼠双微体克隆2（MDM2）、mTOR和NF-κB信号通路。
