依托咪酯对PI3K/AKT通路及非小细胞肺癌A549细胞凋亡的影响

doi:10.3969/j.issn.1006-6233.2020.07.003

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摘要 目的:探讨依托咪酯对磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(AKT)通路及非小细胞肺癌A549细胞凋亡的影响。方法:设A549细胞组、5-氟尿嘧啶组、依托咪酯低剂量组、高剂量组;5-氟尿嘧啶组、依托咪酯低剂量组、高剂量组分别加入5-氟尿嘧啶组、不同浓度的依托咪酯,使其最终浓度为100.0μg/mL、100.0μg/mL、200.0μg/mL,培养72h。细胞计数试剂盒-8评估细胞增殖水平,流式细胞仪测定细胞凋亡水平,Transwell室测定细胞侵袭性,RT-PCR法及WEST-BLOT法测定细胞磷酸化PI3K(p-PI3K)、磷酸化AKT(p-AKT)mRNA和蛋白水平。结果:与A549细胞组比较,5-氟尿嘧啶组、依托咪酯低、高剂量组OD值、存活率水平、穿膜数、p-PI3K、p-AKT mRNA和蛋白降低(P<0.05),凋亡率水平升高(P<0.05);且随着依托咪酯剂量的增加,依托咪酯各剂量组OD值、存活率、穿膜数、p-PI3K、p-AKT mRNA和蛋白逐渐降低(P<0.05),凋亡率水平逐渐升高(P<0.05)。与5-氟尿嘧啶组比较,依托咪酯低剂量组OD值、存活率水平、穿膜数、p-PI3K、p-AKT mRNA和蛋白升高(P<0.05),凋亡率水平降低(P<0.05);依托咪酯高剂量组OD值、存活率水平、穿膜数、p-PI3K、p-AKT mRNA和蛋白降低(P<0.05),凋亡率水平升高(P<0.05)。结论:依托咪酯能抑制肺癌A549细胞增殖、侵袭,促进肺癌A549细胞凋亡;其机制与依托咪酯通过减弱p-PI3K、p-AKT mRNA和蛋白磷酸化水平,进而抑制PI3K/AKT通路的激活传导有关。

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关键词 ：依托咪酯, PI3K/AKT通路, 非小细胞肺癌, 凋亡

Abstract：Objective: To investigate the effect of etomidate on PI3K/AKT pathway and apoptosis of non-small cell lung cancer A549 cell. Methods: A549 cell group, 5-fluorouracil group, etomidate low-dose group and high-dose group were set up. 5-fluorouracil group, etomidate low-dose group and high-dose group were added 5-fluorouracil group and etomidate at different concentrations, and the final concentration was 100.0ug/mL, 100.0ug/mL and 200.0ug/mL for 72 hours. Cell proliferation level was assessed by cell counting kit-8, apoptotic level was measured by flow cytometry, cell invasiveness was measured by Transwell chamber, p-PI3K, p-AKT mRNA and protein levels were measured by RT-PCR and WEST-BLOT. Results: Compared with A549 cell group, the OD value, survival rate, number of perforation, p-PI3K, p-AKT gene and protein were significantly decreased in 5-fluorouracil group, low-dose and high-dose etomidate group(P<0.05), apoptotic rate were significantly increased(P<0.05). And with the increase of etomidate dosage, the OD value, survival rate, number of perforation, p-PI3K, p-AKT gene and protein were gradually decreased (P<0.05), apoptotic rate were gradually increased (P<0.05). Compared with 5-fluorouracil group, the OD value, survival rate, number of perforations, p-PI3K, p-AKT mRNA and protein in low-dose etomidate group were significantly increased(P<0.05), and apoptotic rate were significantly decreased (P<0.05); while the OD value, survival rate, number of perforation, p-PI3K, p-AKT mRNA and protein in high-dose etomidate group were significantly decreased(P<0.05), and apoptotic rate were significantly increased(P<0.05). Conclusion: Etomidate can inhibit the proliferation and invasion of lung cancer A549 cells and promote the apoptosis of lung cancer A549 cells. Its mechanism is related to the inhibition of PI3K/AKT pathway activation and transmission by reducing the levels of p-PI3K, p-AKT mRNA and protein phosphorylation by etomidate.

Key words： Etomidate PI3K/AKT pathway Non-small cell lung cancer Apoptosis

基金资助:海南省卫生计生行业科研项目,(编号:18A200041)

通讯作者: 徐夏

引用本文:

杜佳楠, 戴勤学, 容凤娇, 徐夏. 依托咪酯对PI3K/AKT通路及非小细胞肺癌A549细胞凋亡的影响[J]. 河北医学, 2020, 26(7): 1066-1071.
DU Jia'nan, et al. Effects of Etomidate on PI3K / AKT Pathway and Apoptosis of Non-small Cell Lung Cancer A549 Cells. HeBei Med, 2020, 26(7): 1066-1071.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2020.07.003 或 http://www.hbyxzzs.cn/CN/Y2020/V26/I7/1066

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