Akt特异性抑制剂MK-2206对SGC-7901胃癌细胞增殖的抑制作用研究  

Inhibitory Effects of Specific Akt Inhibitor MK-2206 on the Proliferation of SGC-7901 Gastric Cells

作　　者：张海东[1] 张继国[2] 

机构地区：[1]泰山医学院基础医学院,山东泰安271016 [2]泰山医学院药学院,山东泰安271016

出　　处：《中国药房》2013年第37期3460-3462,共3页China Pharmacy

基　　金：国家自然科学基金资助项目(No.30800422)

摘　　要：目的:研究丝氨酸/苏氨酸蛋白激酶(Akt)抑制剂MK-2206对SGC-7901胃癌细胞增殖的抑制作用及其机制。方法:取对数生长期的SGC-7901胃癌细胞,采用MMT法分别检测0(未给药)、0.5、1.0、2.5、5.0、10、20、30μmol/L的MK-2206作用24 h后细胞的增殖情况;采用流式细胞术分析0、2.5、5.0μmol/L的MK-2206作用24 h后细胞的周期分布;检测0、2.5、10、20μmol/L的MK-2206作用24 h后细胞的凋亡率和细胞周期相关蛋白p21、p27、Cyclin D1以及凋亡相关蛋白Caspase-3、Caspase-8、Caspase-9、多聚腺苷二磷酸核糖聚合酶(PARP)的表达。结果:与未给药比较,5.0、10、20μmol/L的MK-2206均能明显抑制SGC-7901细胞的增殖(P<0.05),且呈浓度依赖性;MK-2206阻滞细胞于G1期。与未给药比较,MK-2206能抑制Cyclin D1表达,上调p21和p27表达,其中20μmol/L的MK-2206作用最强(P<0.05)。SGC-7901细胞经MK-2206作用后,细胞出现明显的凋亡现象,且细胞内Caspase-3、Caspase-8、Caspase-9和PARP的表达均增加,其中20μmol/L的MK-2206作用最强(P<0.05)。结论 :MK-2206对SGC-7901细胞的增殖具有明显的抑制作用,并通过调控Caspase家族成员的活性诱导细胞凋亡。OBJECTIVE ： To study the inhibitory effect and mechanism of serine threonine kinase inhibitor MK-2206 on the pro- liferation of SGC-7901 gastric cancer cells. METHODS： The proliferation of SGC-7901 cells at logarithmic growth phase were de- tected by MTT after treated with 0 （none administration）, 0.5, 1.0, 2.5, 5.0, 10, 20 and 30μmol/L MK-2206 for 24 h. The distri- bution of cell cycle was analyzed by flow cytometry after treated with 0, 2.5 and 5.0 μmol/L MK-2206 for 24 h. Apoptotic rate of SGC-7901 cells after treated with 0, 2.5, 10 and 20μmol/L MK-2206 were detected. The expressions of p21, p27, Cyclin D1, Caspase-3, Caspase-8, Caspase-9 and PARP were determined. RESULTS： Compared with none administration, 5.0, 10 and 20 μmol/L MK-2206 can inhibited the proliferation of SGC-7901 significantly （P〈0.05） in concentration-dependant manner. MK-2206 arrested cell cycle progression at the G1 phase. Compared with none administration, MK-2206 inhibited the expression of Cyclin D1 and up-regulated the expressions of p21 and p27, especially by 20μmol/L MK-2206 （P〈0.05）. MK-2206 treatment substantially induced the apoptosis of SGC-7901 cells and increased the expressions of Caspase-3, Caspase-8, Caspase-9 and PARP, especially by 20μmol/L MK-2206 （P〈0.05）. CONCLUSIONS： MK-2206 can inhibit the proliferation of SGC-7901 cells significantly and in- duce cell apoptosis by regulating the activities of Caspase family.

关 键 词：丝氨酸 苏氨酸蛋白激酶抑制剂MK-2206 SGC-7901胃癌细胞 增殖 

分 类 号：R965[医药卫生—药理学]