蛋白酪氨酸激酶抑制剂Genistein抑制肺癌细胞A549体外侵袭作用的研究

Protein Tyrosine Kinase Inhibitor Genistein to Suppress Invasion of Human Lung Adenocarcinoma Cell Line A549 in vitro

观察蛋白酪氨酸激酶抑制剂Genistein对人肺腺癌细胞株A549细胞侵袭能力的影响,探讨Genistein抑制肺癌细胞侵袭的可能机制。以不同浓度Genistein(20μmol/L和40μmol/L)作用于A549细胞3 d后,分别用基质胶侵袭模型、黏附基质分析、Transwell小室趋化运动模型、细胞骨架蛋白染色及RT-PCR法来研究药物处理后细胞侵袭、黏附、运动、聚合型骨架蛋白(F-actin)以及基质金属蛋白酶基因表达的改变。经Genistein处理后,A549细胞的F-actin聚合减少,侵袭能力明显下降,趋化运动能力降低,基质金属蛋白酶抑制剂(TIMP-1)基因相对表达量增加,但黏附率没有降低。Genistein可降低肺癌细胞的迁移、侵袭能力。F-actin聚合减少,TIMP-1的相对表达量增加,可能是Genistein抑制肺癌细胞侵袭的机制之一。

The effects of tyrosine protein kinase inhibitor,Genistein,on invasion ability of human lung adenocarcinoma cell line A549 were observed and its possible mechanism was investigated.Three days after A549 cells were reacted with different concentration Genistein（20 μmol/L and 40 μmol/L） the changes of invasion,adhesion,movement and migration,as well as expression of F-actin as well as matrix metalloproteinase genes were studied by matrigel invasion models,adhesion matrix analysis,Transwell chamber chemotactic movement models,cytoskeleton protein staining and RT-PCR respectively after the medicine treatment.The results showed that after treated with Genistein,polymerization of F-actin of A549 cells declined,invasive and moving abilities were significantly reduced,chemotactic movement abilities declined,relative expression of matrix metalloproteinase inhibitor（TIMP-1） increased,however,no reduction of adhesion ratio was found.Therefore,Genistein could decrease the lung cancer cell to migrate and the ability of invasion.The reduction of F-actin polymerization and the increment of relative expression of TIMP-1 might be one of the mechanisms of Genistein to inhibit lung cancer cells to invade.