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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。
AIM: To investigate the inhibitory effect of MK-2206, a serine / threonine protein kinase (Akt) inhibitor, on the proliferation of gastric cancer cell line SGC-7901 and its mechanism. Methods: The cells in logarithmic growth phase SGC-7901 gastric cancer cells were treated with MKT-2206 at 0, 0.5, 1.0, 2.5, 5.0, 10, 20 and 30 μmol / L for 24 h The cell cycle distribution of MK-2206 treated with 0, 2.5 and 5.0 μmol / L of MK-2206 for 24 h was analyzed by flow cytometry. The effect of MK-2206 treated with 0, 2.5, 10 and 20 μmol / (P21, p27, Cyclin D1) and apoptosis related proteins Caspase-3, Caspase-8, Caspase-9 and PARP. Results: MK-2206 at 5.0, 10 and 20 μmol / L significantly inhibited the proliferation of SGC-7901 cells in a dose-dependent manner compared with those of untreated cells (P <0.05) . MK-2206 inhibited the expression of Cyclin D1 and up-regulated the expression of p21 and p27 compared with untreated group, of which MK-2206 at 20μmol / L had the strongest effect (P <0.05). After MK-2206 treatment, SGC-7901 cells showed obvious apoptosis, and the expression of Caspase-3, Caspase-8, Caspase-9 and PARP increased in all cells, especially 20μmol / L MK- Strong (P <0.05). Conclusion: MK-2206 can significantly inhibit the proliferation of SGC-7901 cells and induce apoptosis by regulating the activity of Caspase family members.