β-拉帕醌对胃癌细胞生长与侵袭的抑制作用及机制

摘要

Purpose To investigate the effects ofβ-1apachone on inhibition of pro1iferation and migration and induction of apoptosis in gastric cancer ce11s in vitro. Methods The ce11 viabi1ity was detected using MTT and co1ony formation assay,the migration abi1ity was determined using scratch assay method,and the apoptosis was examined using f1ow cytometry. Meanwhi1e,the expression of biomarkers of pro1iferation,EMT markers andapoptosiswere detected using Western b1ot ana1ysis. Results β-1apachone cou1d significant1y inhibit the pro1iferation of SGC-7901 and AGS gastric cancer ce11s( P<0. 05),and down-regu1ate the expression 1eve1s of Skp2 and DEK pro-teins. β-1apachonecou1d a1so inhibited the invasion and moti1ity of gastric cancer ce11s via down-regu1ating the expression 1eve1s of MMP-2/9 and Ezrin proteins and up-regu1ating the epithe1ia1 markers. In addition,β-1apachone enhanced the apoptosis of gastric canc-er ce11s,down-regu1ation of BCL-2/Bax ratio and up-regu1ation of activated Caspase-3/8/9. Conclusions β-1apachone can effective1y inhibit the pro1iferation and induce the apoptosis of gastric cancer ce11s,and inhibit the migration of gastric cancer ce11s via MMPs and EMT pathways.%目的：探讨β-拉帕醌体外抑制胃癌细胞增殖和迁移及诱导凋亡的作用及机制。方法应用噻唑蓝（ MTT）及平板克隆实验检测β-拉帕醌对SGC-7901与AGS胃癌细胞增殖的影响，划痕实验检测β-拉帕醌抑制胃癌细胞的迁移能力，流式细胞术检测β-拉帕醌诱导胃癌细胞凋亡的作用。应用Western b1ot法检测β-拉帕醌处理胃癌细胞前后其增殖、迁移、上皮-间质转化（ epithe1ia1-mesenchyma1 transition，EMT）及凋亡分子标志物的变化。结果β-拉帕醌可显著抑制SGC-7901和AGS胃癌细胞的增殖能力，并下调增殖与周期相关Skp2和DEK蛋白的表达（ P均<0.05）；经β-拉帕醌处理后，胃癌细胞的迁移能力明显下降，且显著下调MMP-2/9和Ezrin蛋白以及EMT间质标志物的表达，上调EMT上皮标志物表达水平；另外，β-拉帕醌增加胃癌细胞的凋亡，下调BCL-2/Bax比值以及上调活化型Caspase-3/8/9的表达。结论β-拉帕醌对胃癌细胞有明显的抑制增殖及诱导凋亡的作用，并可通过MMPs和EMT途径抑制胃癌细胞的迁移能力。