[Mechanisms for quercetin in prevention of lung cancer cell growth and metastasis].

To study the effect of quercetin, an inhibitor of matrix metalloproteinases 9 (MMP-9), on the growth and metastasis of lung cancer cells and the underlying mechanisms. We evaluated the inhibitory effect and the inhibitory kinetics of quercetin on MMP-9 by ELISA and enzyme inhibition kinetics, and the inhibitory effect of quercetin on the growth of lung cancer cell (A549) by MTT. The effect of quercetin on levels of MMP-9 (mRNA and protein) and TGF-β1 (protein) in A549 were measured by RT-PCR and Western blot, respectively. The synergistic inhibition effect of quercetin plus TIMP-1 on the growth of lung cancer cell A549 was discussed. Quercetin induced the apoptosis of A549. It was a reversible competitive inhibitor of MMP-9 (half inhibition rate IC50 of 5.25 μmol/L, inhibition constant Ki was 2.18 μmol/L). With the increase in quercetin concentration, the levels of MMP-9 (mRNA and protein) and TGF-β1 (protein) were decreased, and the number of tumor cells on wear filter membrane was reduced. The combination of quercetin (at low concentrations) with TIMP-1 showed synergistic inhibitory effect on the growth of A549 cells. Quercetin is a competitive inhibitor of MMP-9 and could downregulate the expression of MMP-9 and TGF-β1, which plays an important role in A549 apoptosis.目的：探讨基质金属蛋白酶9(matrix metalloproteinases 9，MMP-9)抑制剂槲皮素对肺癌肿瘤细胞的生长和转移抑制的机制。方法：采用酶联免疫吸附测定法和酶抑制动力学方法研究槲皮素对MMP-9的抑制作用和抑制动力学，MTT分析槲皮素及槲皮素联合组织金属蛋白酶抑制剂1(tissue inhibitor of matrix metalloproteinase 1，TIMP-1)对肺癌肿瘤细胞株A549的生长和转移的抑制作用，RT-PCR法和Western印迹研究槲皮素对肺癌肿瘤细胞中MMP-9 mRNA，MMP-9蛋白和TGF-β1蛋白表达水平的影响。结果：槲皮素能够诱导肺癌肿瘤细胞A549的凋亡，槲皮素是一种可逆的竞争型MMP-9抑制剂 (IC50为5.25 µmol/L，抑制常数Ki为2.18 µmol/L)；随着槲皮素摩尔浓度的增加，MMP-9 mRNA、MMP-9蛋白和TGF-β1蛋白表达均呈现降低趋势；经过槲皮素干预后，肿瘤细胞穿过人工基底膜的能力减弱；低摩尔浓度的槲皮素与TIMP-1联合使用对肺癌肿瘤细胞A549的生长的抑制作用具有协同作用。结论：槲皮素是一个竞争性的MMP-9抑制剂，能够诱导MMP-9的活性降低，并导致MMP-9 mRNA，MMP-9蛋白和TGF-β1蛋白表达的降低，最终对肺癌肿瘤细胞株A549的凋亡起重要作用。.