基础医学与临床 ›› 2022, Vol. 42 ›› Issue (1): 56-61.doi: 10.16352/j.issn.1001-6325.2022.01.006

• 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1, 周静1, 娜日苏1, 孙琪1, 许丽艳2, 白春英1*   

  1. 1.赤峰学院 基础医学院 内蒙古人类遗传病研究重点实验室,内蒙古 赤峰 024000;
    2.汕头大学 医学院 潮汕沿海地区高发肿瘤分子生物学广东省高校重点实验室,广东 汕头 515000
  • 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: * 1053801210@qq.com
  • 基金资助:
    国家自然科学基金(81860496);赤峰学院青年基金(cfxyqn201908);赤峰学院大学生创新创业训练计划(2019-09 自治区级);内蒙古自治区高等学校科学技术研究项目(NJZY20203)

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

SHI Tie-wei1, LI Tian-zhu1, ZHOU Jing1, NA Ri-su1, SUN Qi1, XU Li-yan2, BAI Chun-ying1*   

  1. 1. Key Laboratory of Human Genetic Diseases in Inner Mongolia, School of Basic Medicine,Chifeng University, Chifeng 024000;
    2. Key Laboratory of Molecular Biology of High Incidence Tumor in Chaoshan Coastal Area of Guangdong Province, Medical College,Shantou University,Shantou 515000,China
  • Received:2021-03-18 Revised:2021-10-12 Online:2022-01-05 Published:2022-01-05
  • Contact: * 1053801210@qq.com

摘要: 目的 5-脂氧合酶活化蛋白(FLAP)抑制剂MK886对人食管癌细胞系(KYSE-150和TE-3)增殖和凋亡的影响及作用机制。方法 用2.5、5、10、20、40和80 μmol/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(IC50)。流式细胞测量术检测食管癌细胞的细胞周期。Western blot检测细胞凋亡和自噬相关蛋白的表达。结果 人食管癌细胞系(KYSE-150和TE-3)的增殖抑制率随着MK886浓度增加而增强(P<0.05),KYSE-150组的IC50浓度为29.11 μmol/L,TE-3组的IC50浓度为27.47 μmol/L。当MK886浓度增加至25 μmol/L时,食管癌细胞G0/G1期滞后增加明显(P<0.001),MK886处理浓度增加到50 μmol/L时,食管癌细胞G2/M期增加明显(P<0.001和 P<0.05)。MK886处理后食管癌细胞系随着浓度增加, cleaved-caspase-3和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系的增殖,引起凋亡,并影响细胞周期变化。

关键词: 食管癌, 增殖, 凋亡, MK886, 脂氧合酶

Abstract: Objective To investigate the effects of 5-lipoxygenase activating protein (FLAP) inhibitor MK886 on the proliferation and apoptosis of human esophageal carcinoma cell lines (KYSE-150 and TE-3) and to explore the potential mechanism. Methods KYSE-150 and TE-3 cells were treated with MK886(2.5,5,10,20,40 and 80 μmol/L). xCELLigence RTCA system was used to to detect the half maximal inhibitory concentration(IC50)of MK886. The expressions of proteins with apoptosis and autophagy were detected by Western blot and cell cycles were detected by flow cytometry. Results MK886 decreased the proliferation of human esophageal carcinoma cells(KYSE-150 and TE-3) (both P<0.05).IC50 of MK886 in KYSE-150 group was 29.11 μmol/L and in TE-3 group of 27.47 μmol/L.The proportion of G0/G1 phase was increased(both P<0.001)However, in the group treated with concentrations of MK886 50 μmol/L,G2/M phase was increased(P<0.05). The expression of cleaved-caspase-3 and LC-3A/B-Ⅱwere increased with MK886 (both P<0.001). Conclusions MK886 inhibits proliferation of human esophageal carcinoma cell lines and induces apoptosis.

Key words: esophageal carcinoma, proliferation, apoptosis, MK886, lipoxygenase

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