Zhang Xue-Qin, Li Ying, Liu Jing, Zhao Ting-Mei, Zhao Ruo-Xi, Zheng Shi-Gang, Chun Ze, Hu Ya-Dong
Chengdu Institute of Biology,Chinese Academy of Sciences Chengdu 610041,China University of Chinese Academy of Sciences Beijing 100049,China.
Chengdu Institute of Biology,Chinese Academy of Sciences Chengdu 610041,China.
Zhongguo Zhong Yao Za Zhi. 2019 Feb;44(4):765-773. doi: 10.19540/j.cnki.cjcmm.20181031.004.
Dendrobium denneanum have been used for a long time as rare medicinal herbs in traditional Chinese medicine. Our previous works found that ether extract of D. denneanum had higher anticancer activities than alcohol or water extract,thus with better development prospects. Quantitative proteomics based on SILAC technique was used to investigate the anticancer mechanism of D. denneanum on lung tumor cell line A549,and 4 855 proteins were detected in A549 cells. Quantitative proteomics experiments found that 193 proteins of A549 cells were up-regulated,and 44 proteins were down-regulated by ether extract of D. denneanum. Those proteins are associated with synthesis,transport and metabolism of biological macromolecules,chaperone,DNA repair,oxidoreductase,cell adhesion,cell cycle,apoptosis and autophagy. Through the function analysis of differentially expressed proteins,it was inferred that ether extract of D. denneanum caused cell protein metabolism disorder,endoplasmic reticulum stress response,abnormal self-repair mechanism of cells,damage of cell adhesion and proliferation; besides,it caused a dramatic increase in ROS level in A549 cells,and upset the balance of intracellular oxidation reduction system. Affected by the above factors,lung cancer cells initiated apoptosis and autophagy,which accelerated cell death. This research explains the anticancer mechanism of D. denneanum from the perspective of quantitative proteomics,and lays a foundation for future research and development of new anticancer drugs based on ether extract of D. denneanum.
密花石斛作为珍稀中药材在中国传统医学中已有长期应用。我们之前的研究发现,密花石斛的乙醚提取物比乙醇或水提取物具有更高的抗癌活性,因此具有更好的开发前景。基于SILAC技术的定量蛋白质组学被用于研究密花石斛对肺癌细胞系A549的抗癌机制,在A549细胞中检测到4855种蛋白质。定量蛋白质组学实验发现,密花石斛乙醚提取物使A549细胞中193种蛋白质上调,44种蛋白质下调。这些蛋白质与生物大分子的合成、运输和代谢、分子伴侣、DNA修复、氧化还原酶、细胞黏附、细胞周期、凋亡和自噬相关。通过对差异表达蛋白质的功能分析,推测密花石斛乙醚提取物导致细胞蛋白质代谢紊乱、内质网应激反应、细胞自身修复机制异常、细胞黏附及增殖受损;此外,它还使A549细胞中的活性氧水平显著升高,破坏了细胞内氧化还原系统的平衡。受上述因素影响,肺癌细胞启动凋亡和自噬,加速细胞死亡。本研究从定量蛋白质组学角度解释了密花石斛的抗癌机制,为今后基于密花石斛乙醚提取物开发新型抗癌药物奠定了基础。