Abstract:

Objective To detect the effect of quercetin （QUE） on the growth， lung metastasis，cell invasion and migration of transplanted tumor of the human lung cancer A549 cells transplanted tumor in the mice， and to clarify its related mechanism. Methods The mice were divided into control group （no intervention）， positive drug group （5 mg·kg^－1cisplatin） and low， medium and high doses （12.5， 25.0，and 50.0 mg·kg^－1 QUE）of QUE groups.Except for control group，the mice in other groups were constructed transplanted tumor models using A549 cells.The inhibitory rates of tumor weights and inhibitory rates of lung metastasis of mice in various groups were detected after treated for 10 d. The human lung cancer A549 cells were cultured in vitro and divided into normal control group， QUE group， QUE+Runt related transcription factor 3 （Runx3） negative control sequence （si-NC） （UE+si-NC） group， and QUE+Runx3 interference sequence （si-Runx3） （QUE+si-Runx3） group. Real-time fluorescence quantitative PCR （RT-qPCR） method was used to detect the expression levels of Runt mRNA in the A549 cells in various groups； CCK-8 assay was used to detect inhibitory rates of proliferation of cells in various groups； Transwell chamber experiment was used to detect the numbers of invasion and migration cells in various groups； Western blotting method was used to detect the expression levels of Runx3， Wnt3a， β-catenin， matrix metallopeptidase-2 （MMP-2），and matrix metallopeptidase-9 （MMP-9） proteins in cells in various groups. Results Compared with control group， the inhibitory rate of tumor weight， inhibitory rate of lung metastasis and the expression levels of Runx3 protein in transplant tumor tissue of the mice in positive drug group， low， medium and high doses of QUE groups were increased（P<0.05）， and the expression levels of Wnt3a， β-catenin， MMP-2， and MMP-9 proteins were decreased （P<0.05）. Compared with normal control group，the inhibitory rate of proliferation of the A549 cells in QUE group，the expression levels of Runx3 mRNA and protein in the A549 cells in QUE group were significantly increased （P<0.05）， the numbers of invasion and migration cells were decreased （P<0.05），the expression levels of Wnt3a， β-catenin， MMP-2，and MMP-9 proteins in the cells were significantly decreased （P<0.05）. Compared with QUE+si-NC group， the inhibitory rate of proliferation of the A549 cells in QUE group，the expression levels of Runx3 mRNA and protein in the A549 cells in QUE+si-Runx3 group were significantly decreased （P<0.05）， the numbers of invasion and migration cells，the expression levels of Wnt3a， β-catenin， MMP-2，and MMP-9 proteins in the cells were significantly increased （P<0.05）. Conclusion QUE can inhibit the metastasis and invasion of transplanted tumor of the mice， and its mechanism may be related to promoting the Runx3 expression and inhibiting the Wnt/β-catenin signaling pathway， then inhibiting the invasion and migration of the lung cancer A549 cells.

Key words: Quercetin, Lung neoplasm, A549 cells, Cell invasion, Cell migration, Runt related transcription factor 3, Wnt/β-catenin signaling pathway