肿瘤防治研究2023,Vol.50Issue(12):1191-1196,6.DOI:10.3971/j.issn.1000-8578.2023.23.0399
柠檬苦素通过调节JAK2/STAT3信号通路对非小细胞肺癌细胞恶性生物学行为的影响
Influence of Limonin on Malignant Biological Behavior of Non-small Cell Lung Cancer Cells by Regulating JAK2/STAT3 Signaling Pathway
摘要
Abstract
Objective To investigate the influence of limonin on the malignant biological behavior of non-small cell lung cancer(NSCLC)cells by regulating the protein tyrosine kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods CCK-8 method was applied to detect the survival rate of A549 cells treated with different concentrations of limonin(0,5,10,25,50,75,100 μmol/L).A549 cells were separated into normal culture(NC)group,low-dose limonin group(treatment with 10 μmol/L limonin for 24 h),medium-dose limonin group(treatment with 25 μmol/L limonin for 24 h),high-dose limonin group(treatment with 50 μmol/L limonin for 24 h),coumermycin Al group(treatment with 10 μmol/L JAK2 activator coumermycin Al+50 μmol/L limonin for 24 h),and AG490 group(treatment with 10 μmol/L JAK2 inhibitor AG490+50 μmol/L limonin for 24 h).Clone formation assay was applied to detect the clones of each group of cells.Transwell assay was applied to detect cell migration and invasion,and flow cytometry was applied to detect apoptosis.Western blot analysis was applied to detect the protein expression levels of JAK2,p-JAK2,STAT3,p-STAT3,E-cadherin,N-cadherin,and vimentin in each group.Results The viability of A549 cells decreased significantly in a limonin concentration-dependent manner(P<0.05),with IC50 of 45.16±1.66μmol/L.Concentrations of 10,25,and 50 μmol/L were selected for subsequent experiments.The numbers of clones,migration,and invasion of A549 cells and the protein expression levels of IL-6,p-JAK2,p-STAT3,N-cadherin,and vimentin in the low-,medium-,and high-dose limonin groups significantly decreased,compared with those in the NC group,and the apoptosis rate and E-cadherin protein expression significantly increased(P<0.05).The JAK2 activator coumermycin Al attenuated the ability of limonin to inhibit the proliferation,migration,invasion,and other malignant biological behavior of A549 cells and attenuated the apoptosis ability.The JAK2 inhibitor AG490 enhanced the ability of limonin to inhibit the proliferation,migration,invasion,and other malignant biological behavior of A549 cells and enhanced the apoptosis ability.Conclusion Limonin can inhibit the malignant biological behavior of NSCLC cells,such as proliferation,migration,and invasion,by inhibiting the JAK2/STAT3 pathway.关键词
柠檬苦素/JAK2/STAT3信号通路/非小细胞肺癌/恶性生物学行为Key words
Limonin/JAK2/STAT3 signaling pathway/Non-small cell lung cancer/Malignant biological behavior分类
医药卫生引用本文复制引用
胡会杰,郑晓璐,雷立峰..柠檬苦素通过调节JAK2/STAT3信号通路对非小细胞肺癌细胞恶性生物学行为的影响[J].肿瘤防治研究,2023,50(12):1191-1196,6.基金项目
Medical Science and Technology Tackling Program of Henan Province(No.LHGJ20200849)河南省医学科技攻关计划项目(LHGJ20200849) (No.LHGJ20200849)