Department of Functional Genome Analysis, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120, Heidelberg, Germany; Faculty of Pharmacy, Department of Biochemistry and Molecular Biology, Helwan University, Cairo, Egypt.
J Cell Biochem. 2013 Dec;114(12):2654-65. doi: 10.1002/jcb.24612.
Pancreatic cancer is one of the most lethal human cancers, with almost identical incidence and mortality rates. Curcumin, derived from the rhizome of Curcuma longa, has a long history of use as coloring agent and for a wide variety of disorders. Here, the antiproliferative activity of curcumin and its modulatory effect on gene expression of pancreatic cancer cell lines were investigated. The effect of curcumin on cellular proliferation and viability was monitored by sulphurhodamine B assay. Apoptotic effect was evaluated by flow cytometry and further confirmed by measuring amount of cytoplasmic histone-associated DNA fragments. Analysis of gene expression was performed with and without curcumin treatment using microarray expression profiling techniques. Array results were confirmed by real-time PCR. ingenuity pathway analysis (IPA) has been used to classify the list of differentially expressed genes and to indentify common biomarkergenes modulating the chemopreventive effect of curcumin. Results showed that curcumin induces growth arrest and apoptosis in pancreatic cancer cell lines. Its effect was more obvious on the highly COX-2 expressing cell line. Additionally, the expression of 366 and 356 cancer-related genes, involved in regulation of apoptosis, cell cycle, metastasis, was significantly altered after curcumin treatment in BxPC-3 and MiaPaCa-2 cells, respectively. Our results suggested that up-regulation of the extrinsic apoptotic pathway was among signaling pathways modulating the growth inhibitory effects of curcumin on pancreatic cancer cells. Curcumin effect was mediated through activation of TNFR, CASP 8, CASP3, BID, BAX, and down-regulation of NFκB, NDRG 1, and BCL2L10 genes.
胰腺癌是最致命的人类癌症之一，其发病率和死亡率几乎相同。姜黄素来源于姜黄的根茎，作为着色剂和治疗多种疾病已有很长的历史。在这里，研究了姜黄素的抗增殖活性及其对胰腺癌细胞系基因表达的调节作用。通过硫代罗丹明 B 测定法监测姜黄素对细胞增殖和活力的影响。通过流式细胞术评估凋亡作用，并通过测量细胞质组蛋白相关 DNA 片段的量进一步证实。使用微阵列表达谱技术在有无姜黄素处理的情况下分析基因表达。通过实时 PCR 确认阵列结果。使用 ingenuity 通路分析（IPA）对差异表达基因进行分类，并鉴定调节姜黄素化学预防作用的共同生物标志物基因。结果表明，姜黄素可诱导胰腺癌细胞系生长停滞和凋亡。在 COX-2 高表达的细胞系中，其作用更为明显。此外，在 BxPC-3 和 MiaPaCa-2 细胞中，姜黄素处理后，与细胞凋亡、细胞周期、转移相关的 366 和 356 个癌症相关基因的表达明显改变。我们的结果表明，上调外源性凋亡途径是调节姜黄素对胰腺癌细胞生长抑制作用的信号通路之一。姜黄素的作用是通过激活 TNFR、CASP8、CASP3、BID、BAX 以及下调 NFκB、NDRG1 和 BCL2L10 基因来介导的。
