免疫抑制剂FK506对肺癌细胞增殖和迁移的作用研究

BACKGROUND AND OBJECTIVE: FK506, also named tacrolimus, a new macrolide immunosuppressive agent, has been shown to possess anti-proliferation activities in some cancer cells. The aim of this study was to investigate the effect of FK506 on the cell proliferation and migration of lung cancer cell lines and its mechanism. METHODS: A549 and H1299 cell lines were cultured in vitro. The effect of FK506 on cell viability and DNA synthesis ability of A549 and H1299 were measured by CCK-8 assay and EDU-labeling assay, respectively. Flow cytometry assay was used to detect the cell cycle. The in vitro migration of lung cancer cells was detected by Boyden chamber assay and wound-healing assay after the treatment of FK506. The expression of p27, RB1, CDK4, CDK6 and MMP9 were detected using Western blot. RESULTS: FK506 inhibited cell growth and induced cell cycle arrest in G(0)/G(1) phase in A549 and H1299 cells in a dose-and time-dependent manner. Compared to the control groups, the migration of A549 and H1299 cells treated with FK506 were decreased obviously. Moreover, FK506 increased the expression of P27 and RB1, and reduced the expression of CDK4, CDK6 and MMP9. CONCLUSION: FK506 inhibit the cell growth and migration of lung cancer cells in vitro. The inhibitive effects may be associated with the up-regulation of p27 expression and inhibition CDK4, CDK6 and MMP9 expression.