Ko Yang-Ching, Hsu Shu-Chun, Liu Hsin-Chung, Hsiao Yung-Ting, Hsia Te-Chun, Yang Su-Tso, Hsu Wu-Huei, Chung Jing-Gung
Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C.
Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C.
In Vivo. 2015 Jan-Feb;29(1):83-94.
Lung cancer is the leading cause of cancer-related deaths and new lung cancer cases are continuously emerging around the globe; however, treatment of lung cancer remains unsatisfactory. Demethoxycurcumin (DMC) has been shown to exert cytotoxic effects in human cancer cells via induction of apoptosis. However, the effects of DMC on genetic mechanisms associated with these actions have not been yet elucidated. Human lung cancer NCI-H460 cells were incubated with or without 35 μM of DMC for 24 h and total RNA was extracted for cDNA synthesis labeling and microarray hybridization, followed by fluor-labeled cDNA hybridization on chip. Expression Console software with default Robust Multichip Analysis (RMA) parameters were used for detecting and quantitating the localized concentrations of fluorescent molecules. The GeneGo software was used for investigating key genes involved and their possible interaction pathways. Genes associated with DNA damage and repair, cell-cycle check point and apoptosis could be altered by DMC; in particular, 144 genes were found up-regulated and 179 genes down-regulated in NCI-H460 cells after exposure to DMC. In general, DMC-altered genes may offer information to understand the cytotoxic mechanism of this agent at the genetic level since gene alterations can be useful biomarkers or targets for the diagnosis and treatment of human lung cancer in the future.
肺癌是癌症相关死亡的主要原因,全球范围内新的肺癌病例不断出现;然而,肺癌的治疗仍然不尽人意。去甲氧基姜黄素(DMC)已被证明可通过诱导凋亡在人类癌细胞中发挥细胞毒性作用。然而,DMC对与这些作用相关的遗传机制的影响尚未阐明。将人肺癌NCI-H460细胞在有或无35μM DMC的情况下孵育24小时,提取总RNA用于cDNA合成标记和微阵列杂交,随后在芯片上进行荧光标记的cDNA杂交。使用具有默认稳健多芯片分析(RMA)参数的Expression Console软件检测和定量荧光分子的局部浓度。使用GeneGo软件研究涉及的关键基因及其可能的相互作用途径。与DNA损伤和修复、细胞周期检查点和凋亡相关的基因可能会被DMC改变;特别是,在暴露于DMC后,NCI-H460细胞中发现144个基因上调,179个基因下调。一般来说,DMC改变的基因可能为从遗传水平理解该药物的细胞毒性机制提供信息,因为基因改变可能是未来人类肺癌诊断和治疗的有用生物标志物或靶点。