摘要
目的研究鸟氨酸脱羧酶抗酶抑制因子-1(AZIN-1)小分子抑制剂对非小细胞肺癌的抑制作用及机制。方法通过CCK-8法检测A549细胞增殖;流式细胞术(Annexin V-FITC/PI双染)分析A549细胞凋亡;蛋白质免疫印迹实验检测A549细胞内鸟氨酸脱羧酶(ODC)、鸟氨酸脱羧酶抗酶-1(AZ-1)和AZIN-1的表达;流式细胞术(PI单染)分析A549细胞周期;高效液相色谱法检测A549细胞内总多胺含量。结果AZIN-1小分子抑制剂能够显著抑制A549细胞的增殖,使细胞发生G0/G1周期阻滞,并诱导A549细胞发生凋亡,显著抑制AZIN-1和ODC的表达,干扰细胞内多胺代谢,降低细胞内总多胺含量。结论AZIN-1小分子抑制剂对A549细胞具有显著的生长抑制作用,其作用机制可能与诱导细胞凋亡和干扰多胺代谢有关。
Aim To investigate the inhibitory effect of small molecule inhibitors of ornithine decarboxylase inhibitor 1(AZIN-1)on non-small cell lung cancer and its mechanism.Methods Cell proliferation was detected by Cell Counting Kit-8(CCK-8).Apoptosis was analyzed by flow cytometry(PI/Annexin V-FITC double staining).The expression of ornithine decarboxylase(ODC),ornithine decarboxylase anti-enzyme-1(AZ-1)and AZIN-1 was detected by Western blot.Cell cycle was analyzed by flow cytometry(PI single staining).The total polyamine content in cellswas measured by high performance liquid chromatography(HPLC).Results Small molecule inhibitor of AZIN-1 could significantly inhibit the proliferation of A549 cells,cause G0/G1 cycle arrest,induce apoptosis of A549 cells,inhibit the expression of AZIN-1 and ODC,interfere with intracellular polyamine metabolism,and reduce total polyamine content in cells.Conclusions Small molecule inhibitor of AZIN-1has significant growth inhibitory effect on A549 cells,and its mechanism may be related to the induction of apoptosis and interference with polyamine metabolism.
作者
王顺超
欧洁
孙丽丹
吴红艳
WANG Shun-chao;OU Jie;SUN Li-dan;WU Hong-yan(Dept of Immunology,Medical College,China Three Gorges University,Yichang Hubei 443002,China;Institute of Infection and Injury,China Three Gorges University,Yichang Hubei 443002,China;College of Chemical Engineering and Materials,Quanzhou Normal University, Quanzhou Fujian 362000,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2020年第4期556-561,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81402557)。
关键词
鸟氨酸脱羧酶抗酶抑制因子-1
小分子抑制剂
多胺
非小细胞肺癌
细胞增殖
凋亡
ornithine decarboxylase anti-enzyme inhibitor-1
small molecule inhibitor
polyainines
non-small cell lung cancer
cell proliferation
apoptosis