Luteolin Induces Apoptosis by Up-regulating miR-34a in Human Gastric Cancer Cells
Luteolin Induces Apoptosis by Up-regulating miR-34a in Human Gastric Cancer Cells
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DOI：
10.7785/tcrt.2012.500434
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发表时间：
2015-12-01
影响因子：
2.8
通讯作者：
Liu, Ping
中科院分区：
文献类型：
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作者：
Wu, Hao;Huang, Min;Liu, Ping
木犀草素(39，49，5，7-四羟基黄酮)是一种天然类黄酮，存在于多种蔬菜、水果和中草药中，可抑制不同类型癌症的发生。在这项研究中，我们证明了木犀草素通过抑制凋亡调节蛋白Bcl-2来调节胃癌细胞系的细胞凋亡。四甲基偶氮唑盐和流式细胞仪分析表明，木犀草素可抑制胃癌细胞的增殖并诱导其凋亡。实时定量聚合酶链式反应(qRT-PCR)显示，miR-34a在大多数人原发胃癌组织中的表达下调(8/12，66.7%)，与癌旁、配对的非肿瘤组织相比。靶点分析表明，微小RNA(MiR)-34a直接调控胃癌细胞中的Bcl2，miR-34a过表达可降低胃癌细胞中Bcl2蛋白水平。我们还发现木犀草素上调miR-34a的表达，下调Bcl-2的表达。此外，抗miR-34a寡核苷酸(AMO)可部分逆转木犀草素诱导的胃癌细胞Bcl2表达下调。根据这些结果，我们可以得出结论，木犀草素通过上调miR-34a的表达而部分降低了Bcl一2的表达。本研究首次证明miR-34a通路在木犀草素诱导胃癌细胞凋亡中起重要作用。
Luteolin (39, 49, 5, 7-tetrahydroxyflavone) is a natural flavonoid that exists in several types of vegetables, fruits, and medicinal herbs that inhibits tumorigenesis in different types of cancer. In this study, we demonstrate luteolin-mediated regulation of cell apoptosis in a gastric cancer cell line through inhibition of the apoptosis regulatory protein Bcl-2. MTT and flow cytometric analysis indicate that luteolin inhibits cell proliferation and induces apoptosis in gastric cancer cells. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed that miR-34a expression is downregulated in the majority of human primary gastric cancer tissues (8/12, 66.7%), compared with adjacent, pair-matched non-tumor tissues. Target analysis indicated that micro RNA (miR)-34a directly regulates Bcl-2, and miR-34a overexpression decreased Bcl-2 protein level in gastric cancer cells. We also found that luteolin upregulates miR-34a expression and downregulates Bcl-2 expression. Furthermore, anti-miR-34a oligonucleotides (AMO) partly reverse luteolin-induced Bcl-2 downregulation in gastric cancer cells. Based on these results, we can draw the conclusion that luteolin partly decreases Bcl-2 expression through upregulating miR-34a expression. This study shows for the first time that the miR-34a pathway plays an important role in luteolin-induced apoptosis in gastric cancer cells.