首页> 中文期刊>中国医药导报 >PI3K/AKT及MEK/ERK信号通路抑制剂对结直肠癌血管内皮细胞管道形成的作用

PI3K/AKT及MEK/ERK信号通路抑制剂对结直肠癌血管内皮细胞管道形成的作用

     

摘要

目的:探讨PI3K/AKT信号通路抑制剂(LY294002)及MEK/ERK信号通路抑制剂(PD98059)对结直肠癌血管内皮细胞管道形成的影响。方法实验分为对照组和实验组,其中对照组分正常组和二甲基亚砜(DMSO)组(0.1%DMSO),实验组分PI3K/AKT信号通路抑制剂组LY294002及MEK/ERK信号通路抑制剂组PD98059(实验组设4个浓度梯度),比较结直肠癌血管内皮细胞在不同抑制剂浓度(2.5、5、10、20μmol/L)作用下在Matrigel胶上管道形成的情况,6h后观察并取每个孔上、下、左、右、中5个区域中的图片,测其管道形成的总长度,每组均设3个复孔,数据以均数依标准差表示,采用SPSS 16.0软件进行统计分析,以P<0.05为差异有统计学意义。结果对照组中正常组与DMSO组两者管道形成总长度之间差异无统计学意义[(4.16±0.26)mm比(4.17±0.18)mm],而实验组管道形成总长度较对照组都有明显减少(P<0.05)。其中LY294002浓度在2.5、5、10、20μmol/L管道形成的长度分别为(3.08±0.51)、(2.65±0.24)、(2.02±0.18)、(1.08±0.13)mm,而PD98059管道形成的长度分别为(3.39±0.18)、(2.98±0.12)、(2.53±0.18)、(1.88±0.12)mm,随着浓度的增加,管道形成长度逐渐减少,差异有统计学意义(P<0.05)。 LY294002与PD98059相比,在相同浓度下,LY294002管道形成长度较PD98059减少(P<0.05)。结论PI3K/AKT信号通路抑制剂及ERK/MEK信号通路抑制剂能够明显抑制结直肠癌血管内皮细胞的管道形成,且随着抑制剂浓度的升高,管道形成能力进一步降低,PI3K/AKT信号通路抑制剂抑制肿瘤血管内皮细胞管道形成的能力比ERK/MEK信号通路抑制剂明显。%Objective To study of the effect of PI3K/AKT and ERK/MEK signaling pathway inhibitors on colorectal cancer vascular endothelial cells in tube formationing. Methods The experiment were divided into control group and experiment group, the control group was divided into the normal group and the 0.1%DMSO group, and experiment group was divided into PI3K/AKT signaling pathway inhibitors groups LY294002 and ERK/MEK signaling pathway inhibitors group PD98059 (each group had 4 concentration gradients). Those pipe formation in different inhibitor concentration degree (2.5, 5, 10, 20 μmol/L) were compared, and its inhibitory effects on this micro-vascular forming ability by counting the total length the pictures come from upper, lower, left, right of the tubes formed after six hours were detected. In each hole, each group had three samples, all data were epressed by mean standard deviation, and SPSS16.0 software to conduct statistical analysis was used, it had statistical significance when P< 0.05. Results The length of tubule formation between normal group and DMSO group had no difference [(4.16±0.26) mm vs (4.17±0.18) mm], and the experiment group tubule formation had decreased significantly compared to control group (P<0.05). The length of the pipe forming were (3.08±0.51), (2.65±0.24), (2.02±0.18), (1.08±0.13) mm, when LY294002 concentration were 2.5, 5, 10, 20 μmol/L, and PD98059 were (3.39±0.18), (2.98±0.12), (2.53±0.18), (1.88±0.12) mm, with the increase of concentration, pipe forming length gradually reduced, there were statistical significances (P < 0.05). Compared with PD98059, the pipe forming of LY294002 decreased under the same concentration (P< 0.05). Conclusion PI3K/AKT and ERK/MEK signal pathway inhibitors can inhibit tube formation from colorectal cancer vascular endothelial cells, with the increasing inhibitor concentration, tube formation ability decreased further. PI3K/AKT signaling pathway inhibitors is obvious in inhibit piping formation ability than the MEK/ERK signaling pathway inhibitor.

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