一种新的多酚化合物BJA32531抑制人肝癌HepG_2细胞的增殖和调控miRNA的表达

A New Natural Polyphenol BJA32531 Inhibited the Proliferation and RegulatedmiRNA Expression in Human HepG_2 Hepatocarcinoma Cells

目的:研究从日本蛇菰中分离的天然多酚化合物1,2,6-三-O-没食子酰基-β-D-吡喃葡萄糖(BJA32531)对人肝癌细胞HepG2增殖的抑制作用以及对miRNA表达的影响。方法:采用CCK-8的方法检测HepG2细胞的增殖;用流式细胞法检测HepG2细胞的凋亡;采用miRNA芯片分析方法测定HepG2细胞的miRNA表达以及用RT-PCR的方法验证miRNA的表达。结果:BJA32531以时间和剂量依赖的方式抑制HepG2细胞的增殖;流式细胞结果表明:该化合物能引起HepG2细胞的凋亡。miRNA芯片结果显示,BJA32531能诱导HepG2细胞19个miRNA的表达上调以及85个miRNA的表达下调。RT-PCR验证了化合物诱导的let-7a和miR-10b的上调以及miR-132和miR-125b的下调与芯片的结果一致。结论:BJA32531抗HepG2细胞增殖作用的机理可能与调控miRNA的表达有关。

Objective：To study the effect of 1,2,6-Tri-O-galloyl-β-D-glucopyranose（BJA32531） on the miRNA expression during BJA32531-induced cytotoxicity in human HepG2 hepatocarcinoma cells.Methods：Cell proliferation was assessed using a colorimetric assay（cell counting kit-8）.Apoptosis was assessed by annexin V and propidium iodide staining.The miRNA expression profile of the cancer cells was analyzed by a miRNA array and quantitative real-time PCR.Results： BJA32531 inhibited the cell proliferation and increased apoptosis in HepG2 cancer cells.Cellular exposure to BJA32531 influenced the miRNA expression pattern in the cells,including 19 upregulated and 85 down-regulated miRNAs in the cells.The up-regulations of let-7a and miR-10b as well as the down-regulations of miR-132 and miR-125b were verified to be consistent with the the results of the miRNA array.Conclusion： Our study suggests that the mechanisms by which BJA32531 exerted the antiproliferative effects on HepG2 cancer cells may be related to its regulation of miRNA.