11,12-脱水-二(2-氯乙基)氨基-3,19-环磷酸酯穿心莲内酯抗胃癌细胞增殖、侵袭迁移的机制研究  

Mechanisms of Effect of 11,12-Didehydro-3,19-Cyclophosphate Andrographolide on Proliferation,Invasion and Migration of Gastric Cancer Cells

作　　者：陈淑慧[1,2] 李少华[3] 彭小东[4] 

机构地区：[1]长沙市中心医院肿瘤科,长沙410006 [2]南昌大学研究生院医学部,2011级南昌330006 [3]南昌大学药学院,南昌330006 [4]南昌大学第一附属医院肿瘤科,南昌330006

出　　处：《南昌大学学报（医学版）》2015年第4期22-25,50,共5页Journal of Nanchang University：Medical Sciences

摘　　要：目的研究脱水穿心莲内酯衍生物[11,12-脱水-二(2-氯乙基)氨基-3,19-环磷酸酯穿心莲内酯]抑制胃癌SGC7901细胞增殖、侵袭及迁移的作用,并探讨其可能的作用机制。方法取SGC7901细胞,加入11,12-脱水-二(2-氯乙基)氨基-3,19-环磷酸酯穿心莲内酯中,分别设置20、40、60、80和100μmol·L-1 5个药物浓度组;不加11,12-脱水-二(2-氯乙基)氨基-3,19-环磷酸酯穿心莲内酯的单纯细胞为空白对照组,分别置于培养箱孵育24、48、72h;采用MTT法检测细胞增殖与细胞活力;采用Transwell小室测定24h后SGC7901细胞的侵袭能力,并通过蛋白免疫印迹(Western blot)法检测48h细胞增殖与迁移相关蛋白Akt、p-AKT、JNK、p-JNK、MMP-2、MMP-9的表达情况。结果与空白对照组相比:20、40、60、80和100μmol·L-1 5个药物浓度组能明显抑制SGC7901细胞增殖,并呈时间和浓度依赖性(P<0.01)。空白对照组迁移和侵袭能力无显著变化,11,12-脱水-二(2-氯乙基)氨基-3,19-环磷酸酯穿心莲内酯(40μmol·L-1组)处理SGC7901细胞迁移和侵袭能力较空白对照组明显减弱(P<0.01)。采用11,12-脱水-二(2-氯乙基)氨基-3,19-环磷酸酯穿心莲内酯(40μmol·L-1)处理SGC7901细胞48h后,可明显抑制p-AKT、p-JNK、MMP-2及MMP-9的表达水平。结论 11,12-脱水-二(2-氯乙基)氨基-3,19-环磷酸酯穿心莲内酯可降低胃癌SGC7901细胞的增殖、侵袭和迁移能力,其作用机制可能是通过抑制p-AKT、p-JNK、MMP-2、MMP-9蛋白的表达。Objective To investigate the inhibitory effect of 11,12-didehydro-3,19-cyclophosphate andrographolide on the proliferation,invasion and migration of gastric cancer SGC7901 cells and its mechanism of action.Methods SGC7901 cells were treated with 11,12-didehydro-3,19-cyclophosphate andrographolide（20,40,60,80 and 100μmol·L^-1）for 24,48 and 72hours,respectively.Control cells received the vehicle only.Cell proliferation and viability were measured by MTT assay.After treatment for 24 hours,invasion assay was conducted using transwell chambers.After treatment for 48 hours,the expression of cell proliferation and migration-related proteins Akt,p-AKT,JNK,p-JNK,MMP-2and MMP-9 was detected by Western blot.ResultsCompared with control group,11,12-didehydro-3,19-cyclophosphate andrographolide treatment significantly inhibited the proliferation of SGC7901 cells in a time-and concentration-dependent manner（P〈0.01）.Furthermore,treatment with 11,12-didehydro-3,19-cyclophosphate andrographolide（40μmol·L^-1）significantly decreased the migration and invasion of SGC7901 cells,compared with control group（P〈0.01）.Moreover,treatment with 11,12-didehydro-3,19-cyclophosphate andrographolide（40μmol·L^-1）for 48 hours significantly reduced the expression of p-AKT,p-JNK,MMP-2and MMP-9,compared with control group.Conclusion The treatment with 11,12-didehydro-3,19-cyclophosphate andrographolide can decrease the proliferation,invasion and migration of gastric cancer SGC7901 cells through inhibiting the expression of p-AKT,pJNK,MMP-2and MMP-9proteins.

关 键 词：脱水穿心莲内酯环磷酸酯衍生物 SGC7901细胞 增殖 侵袭迁移 Akt JNK MMP-2 MMP-9 

分 类 号：R914.5[医药卫生—药物化学]