PI3K抑制剂ZSTK-474对结直肠癌细胞增殖和侵袭的影响

目的:探讨PI3K抑制剂ZSTK-474对结直肠癌细胞增殖和侵袭的影响。方法:采用不同浓度（0、1、2、4、6、8和10 μmol/L）ZSTK-474处理结直肠癌HT-29和HCT-116细胞24 h和48 h，CCK8法检测细胞增殖活性并计算出ZSTK-474在两株结直肠癌细胞中的半数抑制浓度（IC50）。根据IC50的值选用浓度为4 μmol/L的ZSTK-474作用HT-29和HCT-116细胞24 h，同时设置加入等量的0.1%DMSO为对照。采用平板克隆形成实验检测细胞增殖，流式细胞仪检测细胞凋亡，qRT-PCR检测细胞PI3K、Akt的mRNA水平，Western blot 检测细胞PI3K、Akt的蛋白水平。结果:ZSTK-474可明显抑制HT-29和HCT-116细胞的增殖，且呈时间和剂量依赖性。ZSTK-474可抑制HT-29和HCT-116细胞的侵袭能力，但不影响其凋亡。ZSTK-474处理HT-29和HCT-116细胞24 h后，PI3K和Akt的mRNA和蛋白表达水平均显著下降。结论:ZSTK-474能够抑制结直肠癌细胞增殖，并且能抑制其侵袭。

Effect of PI3K inhibitor ZSTK-474 on proliferation and invasion of colorectal cancer cells

Objective:Toinvestigate the effect of ZSTK-474 on proliferation and invasion of colorectal cancer cells.Methods:HT-29 and HCT-116 cells were treated with different concentrations(0，1，2，4，6，8 and 10 μmol/L) of ZSTK-474 for 24 h and 48 h.CCK8 assay was used to determine the cell viability,and the half ihhibitory concentration (IC50) was calculated.HT-29 and HCT-116 cells treated with 4 μmol/L ZSTK-474 were used as the experimental group according to the value of IC50,and those treated with 0.1% DMSO as the control group.The cell proliferation was detected by Colony-forming assay.Cell apoptosis was examined by flow cytometry,and cell invasion was evaluated by Transwell assay.The mRNA expression of PI3K and Akt were determined by qRT-PCR,and the protein expression of PI3K and Akt were assessed by Western blot.Results:ZSTK-474 significantly inhibited the proliferation and invasion of HT-29 and HCT-116 cells in a time and dose dependent manner.ZSTK-474 did not affect the apoptosis of HT-29 and HCT-116 cells.The mRNA and protein expression of PI3K and Akt were inhibited in HT-29 and HCT-116 cells with ZSTK-474 treated for 24 h.Conclusion:ZSTK-474 inhibits colorectal cancer cells proliferation and invasion in vitro．