Analysis of gene expression profiles in human HL-60 cell exposed to cantharidin using cDNA microarray
Analysis of gene expression profiles in human HL-60 cell exposed to cantharidin using cDNA microarray
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DOI：
10.1002/ijc.11405
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发表时间：
2004-01-10
影响因子：
6.4
通讯作者：
Rui, YC
中科院分区：
文献类型：
--
作者：
Zhang, JP;Ying, K;Rui, YC
斑蝥素是一种天然毒素，具有抗肿瘤特性，可引起白细胞增多，并增加肿瘤细胞对其他化疗药物的敏感性。然而，关于灯盏花素对人类癌细胞的分子药理学机制的信息有限。我们已经使用cDNA微阵列，以确定基因表达的变化，HL-60早幼粒白血病细胞暴露于藜芦醇苷。斑蝥素处理的细胞不仅降低了编码参与DNA复制的蛋白质的基因的表达（例如，DNA聚合酶δ）、DNA修复（例如，FANCG、ERCC）、能量代谢（例如，异柠檬酸脱氢酶α，ADP/ATP移位酶），而且降低了编码具有致癌活性的蛋白质的基因的表达（例如，c-myc，GT3）或显示肿瘤特异性表达（例如，磷脂酰肌醇3-激酶）。相反，这些处理的细胞过表达编码细胞内和分泌的生长抑制蛋白的几种基因（例如，BTG 2，MCP-3）以及促凋亡基因（例如，ATL衍生的PMA响应肽）。我们的研究结果表明，在功能上与细胞增殖或凋亡相关的特定基因的改变可能是负责藜芦定介导的细胞毒性。我们还发现，HL-60细胞暴露于藜芦苷导致多药耐药相关蛋白基因（例如，ABCA 3，MOAT-B），这表明灯盏花素可用作肿瘤治疗增敏剂，以及在调节细胞因子产生和炎症反应中基因表达的增加（例如，NFIL-3，N-甲酰肽受体），这可能部分解释了对白细胞增多的刺激作用。我们的数据提供了新的见解的分子机制的紫花苜蓿苷。(C)2003 Wiley-Liss，Inc.
Cantharidin is a natural toxin that has antitumor properties and causes leukocytosis as well as increasing sensitivity of tumor cells resistant to other chemotherapeutic agents. There is limited information, however, on the molecular pharmacological mechanisms of cantharidin on human cancer cells. We have used cDNA microarrays to identify gene expression changes in HL-60 promyeloid leukemia cells exposed to cantharidin. Cantharidin-treated cells not only decreased expression of genes coding for proteins involved in DNA replication (e.g., DNA polymerase delta), DNA repair (e.g., FANCG, ERCC), energy metabolism (e.g., isocitrate dehydrogenase alpha, ADP/ATP translocase), but also decreased expression of genes coding for proteins that have oncogenic activity (e.g., c-myc, GTPase) or show tumor-specific expression (e.g., phosphatidylinositol 3-kinase). In contrast, these treated cells overexpressed several genes that encode intracellular and secreted growth-inhibitory proteins (e.g., BTG2, MCP-3) as well as proapoptotic genes (e.g., ATL-derived PMA-responsive peptide). Our findings suggest that alterations in specific genes functionally related to cell proliferation or apoptosis may be responsible for cantharidin-mediated cytotoxicity. We also found that exposure of HL-60 cells to cantharidin resulted in the decreased expression of multidrug resistance-associated protein genes (e.g., ABCA3, MOAT-B), suggesting that cantharidin may be used as an oncotherapy sensitizer, and the increased expression of genes in modulating cytokine production and inflammatory response (e.g., NFIL-3, N-formylpeptide receptor), which may partly explain the stimulating effects on leukocytosis. Our data provide new insight into the molecular mechanisms of cantharidin. (C) 2003 Wiley-Liss, Inc.