二氢杨梅素抑制人乳腺癌细胞侵袭和下调MMP-2/-9蛋白表达研究

藤茶活性成分二氢杨梅素(3, 5, 7, 3′, 4′, 5′-六羟基-2, 3-二氢黄酮醇，DMY)体外对几种癌细胞具有抗增殖作用，但机制尚未完全清楚．本文研究DMY对人高转移型乳腺癌MDA-MB-231细胞侵袭的影响，并探讨可能的机制．用MTT法检测DMY对MDA-MB-231细胞的增殖抑制率；明胶酶谱分析明胶酶活力；基质金属蛋白酶(MMP-2/-9)的基因表达水平和蛋白质表达水平分别利用实时定量PCR和Western blot分析进行检测．Transwell模型检测DMY对肿瘤细胞侵袭的影响．结果显示，DMY以剂量依赖方式抑制MDA-MB-231细胞的增殖，作用48 h的IC50为73.6 mg/L．DMY显著抑制明胶酶活性和MMP-2/-9蛋白表达，并抑制MMP-2/-9 的mRNA表达水平．此外，DMY不依赖细胞毒作用和以剂量依赖方式抑制MDA- MB-231细胞的侵袭．这些结果提示：DMY能显著抑制人乳腺癌MDA-MB-231细胞的侵袭和增殖, 其侵袭抑制的机制可能与其下调MMP-2/-9蛋白表达水平相关．

Dihydromyricetin Inhibits Cell Invasion and Down-regulates MMP-2/-9 Protein Expression Levels in Human Breast Cancer Cells

Dihydromyricetin(3,5,7,3′,4′,5′-hexahydroxy-2,3-dihydroflavonol,DMY) isolated from Ampelopsis grossedentata is known to have an anti-proliferative effect in vitro on a few cancer cells.However,the exact mechanisms retain unclear.The aim of this article was to study the effect of DMY on cell invasion of highly metastatic human breast cancer MDA-MB-231 cells,and investigate the possible mechanisms.The anti-proliferation effect of DMY on MDA-MB-231 cells was determined by the MTT assay.The gelatinolytic activity was assessed by gelatin zymography.The mRNA and the protein expression levels of MMP-2/-9 were evaluated by Real-time PCR and Western blot assay,respectively.The effect of DMY on cell invasion was observed by a transwell model.Results indicated that DMY inhibited the proliferation of MDA-MB-231 cells in a dose-dependent manner,and the IC50 value was about 73.6 mg/L after treated by DMY for 48 h.DMY suppressesed gelatinase activity and MMP-2/-9 protein expression levels in a dose-dependent manner,and restrained MMP-2/-9 mRNA expression levels.In addition,DMY inhibited the invasion of MDA-MB-231 cells in a dose-dependent manner without cytotoxicity against the cancer cells.DMY can inhibit proliferation and invasion of MDA-MB-231 cells,and invasion inhibition may be related to the down-regulation of the expression levels of MMP-2/-9 proteins.