基础医学与临床 ›› 2022, Vol. 42 ›› Issue (1): 56-61.

• 研究论文 • 上一篇    下一篇

5-脂氧合酶激活蛋白抑制剂MK886对人食管癌细胞系增殖和凋亡的影响

史铁伟1,李天柱2,周静3,娜日苏4,孙琪1,许丽艳5,白春英2   

  1. 1. 赤峰学院基础医学院
    2. 内蒙古赤峰市赤峰学院医学院
    3. 赤峰学院
    4. 赤峰学院医学院
    5. 汕头大学
  • 收稿日期:2021-03-18 修回日期:2021-10-12 出版日期:2022-01-05 发布日期:2022-01-05
  • 通讯作者: 白春英 E-mail:1053801210@qq.com
  • 基金资助:
    国家自然科学基金项目;赤峰学院青年基金项目;赤峰学院大学生创新创业训练计划项目;内蒙古自治区高等学校科学技术研究项目

Effects of 5-lipoxygenase activating protein inhibitor MK886 on proliferation and apoptosis of human esophageal cancer cell lines

  • Received:2021-03-18 Revised:2021-10-12 Online:2022-01-05 Published:2022-01-05
  • Supported by:
    National Natural Science Foundation of China;Funds for Young of Chifeng University;Chifeng University Students' innovation and entrepreneurship training program;Scientific and technological research projects of universities in Inner Mongolia Autonomous Region

摘要: 目的 探讨5-脂氧合酶活化蛋白(5-lipoxygenase activating protein,FLAP)抑制剂MK886对食管癌细胞增殖和凋亡的影响及作用机制。方法 用不同浓度2.5、5、10、20、40、80μmol/L的MK886干预体外培养的KYSE-150和TE-3细胞; xCELLigence RTCA系统实时测定细胞增殖抑制率,同时确定半数抑制浓度(half maximal inhibitory concentration,IC50)。FCM法检测不同浓度药物处理后的食管癌细胞的细胞周期变化水平。蛋白质印迹法检测不同浓度药物处理后细胞凋亡和自噬相关蛋白的表达水平。结果 MK886对KYSE-150和TE-3细胞的增殖抑制率随着浓度增加而增强(P<0.05)。KYSE-150处理的IC50浓度为29.11μmol/L,TE-3处理的IC50浓度为27.47μmol/L。MK-886处理浓度增加到25μmol/L,食管癌细胞G0/G1期滞后增加明显(P<0.001),MK-886处理浓度增加到50μmol/L,食管癌细胞G2/M期增加明显(P<0.005)。蛋白质印迹检测MK-886处理后食管癌细胞随着浓度增加,PAPR蛋白表达水平无明显差异,Caspase-9表达水平没有增强,Cleaved caspase-3表达水平增强(P<0.001),LC-3A/B-Ⅱ蛋白表达水平增强(P<0.001)。结论 MK886能抑制人食管癌细胞KYSE-150和TE-3的增殖,引起凋亡,其机制与改变细胞周期和Casepase-3凋亡机制有关,但是高浓度的药物处理会引起食管癌细胞的自噬反应,给临床用药提供一定理论参考。

关键词: 食管癌, 细胞增殖, 细胞凋亡, MK886, 脂氧合酶

Abstract: Objective To investigate the effects of MK886,a 5-LOX-activating protein(FLAP)inhibitor on the proliferation and apoptosis of human esophageal carcinoma cells KYSE-150 and TE-3,and to explore the possible mechanism.Methods KYSE-150 and TE-3 cells were treated with different concentrations of MK886(2.5,5,10,20,40 and 80μmol/L).Used xCELLigence RTCA monitor real-time the growth of cells to detect the half maximal inhibitory concentration(IC50)of MK886 in various cells.After the treatment with different concentrations of MK886,the expression levels of proteins with apoptosis and autophagy were detected by Western blotting,and cell cycle were detected by flow cytometry.Result MK886 decreased the proliferation of human esophageal carcinoma cells KYSE-150 and TE-3 (both P<0.05).The IC50 values of MK886 in KYSE-150 is 29.11μmol/L,in TE-3 is 27.47μmol /L.The proportion of KYSE-150 and TE-3 cells treated with concentrations of MK-886 25μmol/L,G0/G1 phase were increased(both P<0.001)however treated with concentrations of MK-886 50μmol/L,G2/M phase were increased(both P<0.005). Did not detected the proteins expression levels of PARP, caspase-9 were increased with different concentrations of MK886.The expression levels of cleaved Caspase-3 and LC-3A/B-Ⅱwere detected increased with MK886 (both P<0.001).Conclusion MK886 can inhibit the proliferation of KYSE-150 and TE-3 cells induce apoptosis and cell cycle,however autophagy induced by high concentrations MK886,provided the theoretical reference for clinical medication.

Key words: esophageal carcinoma, cell proliferation, apoptosis, MK886, Lipoxygenase

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