Li Huiping, Wu Hongjin, Zhang Hongfang, Li Ying, Li Shuang, Hou Qiang, Wu Shixiu, Yang Shuan-Ying
1 Department of Respiratory Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
2 Department of Emergency Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Tumour Biol. 2017 Jun;39(6):1010428317705334. doi: 10.1177/1010428317705334.
Curcumin is a potent anti-cancer drug in several types of human cancers. Despite of several preclinical and clinical studies of curcumin, the precise mechanism of curcumin in cancer prevention has remained unclear. In our study, we for the first time investigated whole transcriptome alteration in A549 non-small cell lung cancer (NSCLC) cell lines after treatment with curcumin using RNA sequencing. We found that lots of genes and signaling pathways were significantly altered after curcumin treatment in A549 cells. With bioinformatics approaches (gene ontology, Kyoto Encyclopedia of Genes and Genomes, and STRING), we found that those curcumin altered genes were not only the genes that induce cell death but also those extracellular matrix receptors and mitogen-activated protein kinase signaling pathway genes which regulate cell migration and proliferation. Among those significantly altered genes, eight genes ( COL1A1, COL4A1, COL5A1, LAMA5, ITGA3, ITGA2B, DDIT3, and DUSP1) were further examined by quantitative reverse transcription polymerase chain reaction and western blot analysis in four non-small cell lung cancer cell lines. Both in cell lines and in mouse model, the extracellular matrix receptors including the integrin ( ITGA3 and ITGA2B), collagen ( COL5A1), and laminin ( LAMA5) were significantly inhibited by curcumin at messenger RNA and protein levels. Functional studies confirmed that curcumin not only induced A549 cell death but also repressed cell proliferation and migration by regulating extracellular matrix receptors. Collectively, our study suggests that curcumin may be used as a promising drug candidate for intervening lung cancer in future studies.
姜黄素是一种对多种人类癌症有效的抗癌药物。尽管对姜黄素进行了多项临床前和临床研究，但其在癌症预防中的精确机制仍不清楚。在我们的研究中，我们首次使用RNA测序研究了姜黄素处理后A549非小细胞肺癌（NSCLC）细胞系中的全转录组变化。我们发现，姜黄素处理后A549细胞中的许多基因和信号通路发生了显著改变。通过生物信息学方法（基因本体论、京都基因与基因组百科全书和STRING），我们发现那些被姜黄素改变的基因不仅包括诱导细胞死亡的基因，还包括调节细胞迁移和增殖的细胞外基质受体和丝裂原活化蛋白激酶信号通路基因。在那些显著改变的基因中，通过定量逆转录聚合酶链反应和蛋白质印迹分析，在四种非小细胞肺癌细胞系中进一步检测了八个基因（COL1A1、COL4A1、COL5A1、LAMA5、ITGA3、ITGA2B、DDIT3和DUSP1）。在细胞系和小鼠模型中，包括整合素（ITGA3和ITGA2B）、胶原蛋白（COL5A1）和层粘连蛋白（LAMA5）在内的细胞外基质受体在信使RNA和蛋白质水平上均被姜黄素显著抑制。功能研究证实，姜黄素不仅诱导A549细胞死亡，还通过调节细胞外基质受体抑制细胞增殖和迁移。总的来说，我们的研究表明，姜黄素可能是未来研究中干预肺癌的一种有前景的候选药物。
