Abstract:
Objective This study aimed to investigate the effects of Src kinase inhibitor PP2 in the metastasis of human breast cancer MCF-7 cells and its related mechanisms.
Methods MCF-7 cells were treated with PP2 for 48 h to detect the changes in cell adhesion, invasion, and cycle.In particular, western blot and real-time polymerase chain reaction assays were performed to determine the expression of metastasis-related gene.Reporter gene assay was performed to examine the promoter transcriptional activity of nuclear factor kappaB(NF-κB) and transcription factor AP-1(AP-1).
Results PP2 could downregulate Src activities in MCF-7 cells after these cells were treated with PP2 for 48 h.After these cells were treated with 2.5 and 5 μM PP2, the cell adhesion potentials of MCF-7 cells were decreased by 63.4% and 34.7%, respectively.The cell invasion potentials were also decreased by 44.3% and 20.2%, respectively.The cell cycle was inhibited at the G0/G1 phase.CD44, MMP-2/9, and p-β-catenin expressions were decreased, whereas E-cadherin expression was increased.The promoter transcriptional activities of AP-1 were decreased by 64.5%(2.5 μM PP2) and 37.9%(5 μM PP2).The promoter transcriptional activities of NF-κB were also decreased by 55.7%(2.5 μM PP2) and 31.8%(5 μM PP2).
Conclusion A close relationship was found between Src kinase and the metastasis potential of human breast cancer MCF-7 cells.The inhibition of Src kinase activity could suppress tumor metastasis.
下载: