丹酚酸A对食管癌细胞增殖与凋亡的影响及其机制  

Effect of salvianolic acid A on the proliferation and apoptosis in esophageal cancer cells and the underlying mechanisms

作　　者：尹小菲 冯艳艳 康文全[1] YIN Xiaofei;FENG Yanyan;KANGWenquan(Department of Gastroenterology,Nanshan People’s Hospital,Shenzhen Guangdong 518052,China)

机构地区：[1]深圳市南山区人民医院消化内科,广东深圳518052

出　　处：《中南大学学报（医学版）》2020年第11期1269-1275,共7页Journal of Central South University ：Medical Science

基　　金：广东省自然科学基金(201775320)。

摘　　要：目的:探讨丹酚酸A(salvianolic acid A,SalA)对食管癌细胞KYSE-150增殖、凋亡的影响及其相关的作用机制。方法:将细胞随机分为对照组、10μmol/L SalA组、25μmol/L SalA组、50μmol/L SalA组。采用细胞计数试剂盒(cell counting kit-8,CCK-8)检测细胞增殖活性,流式细胞术检测细胞周期分布和细胞凋亡;采用蛋白质印迹法检测细胞增殖标志物Ki-67,细胞周期素D1(cyclin D1),细胞周期蛋白依赖性激酶4(cyclin-dependent kinase,CDK4),CDK6,B细胞淋巴瘤-2(B-cell lymphoma-2,Bcl-2),Bcl-2相关X(Bcl-2 associated X,Bax),活化半胱氨酸天冬氨酸蛋白酶(cleaved-caspase-9,cl-caspase-9),cl-caspase-3,磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K),磷酸化蛋白激酶B(phosphorylated protein kinase B,P-Akt)和哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)的表达水平。结果:与对照组相比,SalA各浓度组细胞增殖活性均显著降低(均P<0.01);处于G1期的细胞显著增加,S期细胞显著减少(均P<0.01);细胞凋亡率均显著升高(均P<0.01);SalA各浓度组细胞中Ki-67,cyclin D1,CDK4,CDK6,Bcl-2,PI3K,p-Akt和mTOR的表达水平均显著降低;而p21,Bax,cl-caspase-9和clcaspase-3的表达水平均显著上升,差异均有统计学意义(均P<0.01)。结论:SalA能抑制食管癌细胞KYSE-150增殖,诱导细胞G1期阻滞和细胞凋亡,其作用机制可能与抑制PI3K/Akt/mTOR通路的激活有关。Objective:To explore the effect of salvianolic acid A(SalA)on the proliferation and apoptosis in esophageal cancer cell line KYSE-150 and the possible mechanisms.Methods:The esophageal cancer cells were randomly divided into 4 groups:a control group,a 10μmol/L SalA group,a 25μmol/L SalA group,and a 50μmol/L SalA group.Cell counting kit-8(CCK-8)was used to detect the cell proliferation activity.Flow cytometry was used to detect cell cycle distribution and cell apoptosis rate.Western blotting was used to detect the protein expression of cell proliferation maker Ki-67,cyclin D1,cyclindependent kinase 4(CDK4),CDK6,B-cell lymphoma-2(Bcl-2),Bcl-2 associated X(Bax),cleaved-caspase-9,cleaved-caspase-3,phosphatidylinositol 3-kinase(PI3K),phosphorylated protein kinase B(p-Akt)and mechanistic target of rapamycin(mTOR).Results:Compared with the control group,the cell proliferation activity was significantly reduced(P<0.01);the cells in the G1 phase were significantly increased,and the S phase cells were significantly reduced(both P<0.01);the cell apoptosis rate was significantly increased(P<0.01)in the SalA groups at different concentration;the expression levels of Ki-67,cyclin D1,CDK4,CDK6,Bcl-2,PI3K,p-Akt and mTOR were decreased significantly,but the expression levels of p21,Bax,cl-caspase-9 and cl-caspase-3 were increased significantly in the SalA groups at different concentration(all P<0.01).Conclusion:SalA can inhibit the proliferation and induce G1 phase arrest and apoptosis in the esophageal cancer cell line KYSE-150,which may be related to the activation of PI3K/Akt/mTOR signal pathway.

关 键 词：丹酚酸A 食管癌 增殖 细胞周期阻滞 凋亡 

分 类 号：R285[医药卫生—中药学]