Article Abstract

Cyclooxygenase-2 mediates puerarin to inhibit the invasion and metastasis of lung cancer A549 cells

Authors: Yun Zeng, Zheng-Jie Shen, Wen-Zhe Gu, Mian-Hua Wu

Abstract

Background: The mechanisms by which puerarin prevents and treats lung cancer remain largely unknown. We aimed to study the roles of puerarin in the invasion and metastasis of lung cancer A549 cells based on cyclooxygenase-2 (COX-2).
Methods: The effects of different concentrations of puerarin on the proliferation of A549 cells were evaluated. The in vitro and in vivo effects of puerarin on the invasion and metastasis of A549 cells were assessed by Transwell assay and an animal model of tumor lung metastasis respectively. The influence of puerarin on COX-2 in A549 cells was also analyzed in terms of enzymatic activity and tissue level to explore the role of COX-2 in the inhibitory effects of puerarin on cell invasion and metastasis.
Results: Puerarin inhibited the proliferation of A549 cells in time- and dose-dependent manners. Compared with the control group, more cells in the puerarin treatment groups were arrested in the G0/G1 phase, but the proportion of S phase cells decreased. Puerarin blocked the cell cycle dose-dependently. After 24 h of culture with 200 μg/mL puerarin, significantly fewer cells penetrated the basement membrane of Transwell chambers than those in the control group, and the MMP-2/TIMP-2 levels in PUE200, PUE400 and PUE800 groups significantly dropped. For the animal experiments, the puerarin treatment groups had significantly fewer and smaller tumors with pulmonary metastasis than those of the control group. After 24 h of culture with puerarin, like the indomethacin (IN) group, PUE200, PUE400 and PUE800 groups had significantly lower enzymatic activity of COX-2 than that of the control group, but the puerarin treatment groups had similar results. The IN group had lower COX-2 protein expression than that of the control group, but the puerarin treatment groups had similar expressions to that of the control group, indicating that COX-2 protein expression was hardly affected by puerarin in A549 cells. Similar to the IN group, the puerarin treatment groups had significantly lower PGE2 levels than that of the control group (P<0.05). However, there was no significant difference between PUE200, PUE400 and PUE800 groups. The tumors with pulmonary metastasis from the puerarin treatment groups had significantly lighter colors of COX-2 positive cells and particles than those of the control group.
Conclusions: Puerarin inhibited the enzymatic activity of COX-2 in A549 cells and its expression in tumor tissues with pulmonary metastasis. MMP-2/TIMP-2 may be one of the mechanisms by which puerarin inhibits the invasion of A549 cells.

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