莱菔硫烷对膀胱癌细胞增殖抑制作用

Effects of sulforaphane on proliferation of human bladder cancer cells and its mechanism

目的研究丝裂原活化蛋白激酶(MAPKs)和磷脂酰肌醇激酶(PI3K)信号途径在莱菔硫烷(sulforaphane,SFN)抑制膀胱癌细胞增殖中的作用。方法噻唑蓝(MTT)法测定膀胱癌细胞的增殖作用,用实时定量PCR方法(re-al time-PCR)测定对环氧化酶(COX-2)mRNA的影响。结果 5～20μmol/L莱菔硫烷能明显抑制膀胱癌细胞的体外增殖、COX-2 mRNA表达;SB202190或LY294002预处理T24细胞,能明显降低莱菔硫烷对T24细胞增殖的抑制作用,提高细胞存活率;SB202190预处理T24细胞1h能完全阻断莱菔硫烷对COX-2 mRNA的抑制作用,而LY294002不影响莱菔硫烷对COX-2 mRNA的抑制作用。结论莱菔硫烷可能是通过活化p38激酶途径和PI3K激酶途径抑制膀胱癌细胞生长,p38激酶信号途径在SFN抑制COX-2 mRNA中起关键作用。

Objective To sutdy the effects of mitogen activated protein kinase（MAPK） and phosphatidy linositol 3-kinase（PI3K） on the inhibition of human bladder cancer cell proliferation induced by sulforaphane（SFN）.MethodsMethyl thiazolyl tetrazolium（MTT） assay was used to detect T24 cell proliferation.The level of cyclooxygenase-2（COX-2） mRNA was determined by quantitative real-time PCR.Results SFN（5-20 μmol/L） significantly suppressed the proliferation and the expression of COX-2 mRNA.Pretreatment with inhibitor SB202190 or LY294002,anti-proliferation of SFN on T24 cells was remarkably attenuated by the increase of cell viability.Inhibitor SB202190,but not LY294002,could thoroughly masked the level of COX-2 mRNA downregulated by SFN.Conclusion The results suggest that p38MAPK and PI3K signal pathway are involved in the inhibitory effect of SFN on T24 cells and p38MAPK plays a key role in the inhibition of COX-2 mRNA by SFN.