Influence of Limonin on Malignant Biological Behavior of Non-small Cell Lung Cancer Cells by Regulating JAK2/STAT3 Signaling Pathway
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 dete...
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| Format: | Article |
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Magazine House of Cancer Research on Prevention and Treatment
2023-12-01
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| Series: | Zhongliu Fangzhi Yanjiu |
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| Online Access: | http://www.zlfzyj.com/EN/10.3971/j.issn.1000-8578.2023.23.0399 |
| _version_ | 1797372848216473600 |
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| author | HU Huijie ZHENG Xiaolu LEI Lifeng |
| author_facet | HU Huijie ZHENG Xiaolu LEI Lifeng |
| author_sort | HU Huijie |
| collection | DOAJ |
| description | 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 A1 group (treatment with 10 μmol/L JAK2 activator coumermycin A1+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±1.66 μmol/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 A1 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. |
| first_indexed | 2024-03-08T18:41:45Z |
| format | Article |
| id | doaj.art-52ef41da65204fadaa7b2bc418cd2c5b |
| institution | Directory Open Access Journal |
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| language | zho |
| last_indexed | 2024-03-08T18:41:45Z |
| publishDate | 2023-12-01 |
| publisher | Magazine House of Cancer Research on Prevention and Treatment |
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| spelling | doaj.art-52ef41da65204fadaa7b2bc418cd2c5b2023-12-29T06:02:13ZzhoMagazine House of Cancer Research on Prevention and TreatmentZhongliu Fangzhi Yanjiu1000-85782023-12-0150121191119610.3971/j.issn.1000-8578.2023.23.03998578.2023.23.0399Influence of Limonin on Malignant Biological Behavior of Non-small Cell Lung Cancer Cells by Regulating JAK2/STAT3 Signaling PathwayHU Huijie0ZHENG Xiaolu1LEI Lifeng2Department of Respiratory and Critical Illness Medicine, General Hospital of Pingmei Shenma Medical Group, Pingdingshan 467000, ChinaDepartment of Respiratory and Critical Illness Medicine, General Hospital of Pingmei Shenma Medical Group, Pingdingshan 467000, ChinaDepartment of Respiratory and Critical Illness Medicine, General Hospital of Pingmei Shenma Medical Group, Pingdingshan 467000, ChinaObjective 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 A1 group (treatment with 10 μmol/L JAK2 activator coumermycin A1+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±1.66 μmol/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 A1 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.http://www.zlfzyj.com/EN/10.3971/j.issn.1000-8578.2023.23.0399limoninjak2/stat3 signaling pathwaynon-small cell lung cancermalignant biological behavior |
| spellingShingle | HU Huijie ZHENG Xiaolu LEI Lifeng Influence of Limonin on Malignant Biological Behavior of Non-small Cell Lung Cancer Cells by Regulating JAK2/STAT3 Signaling Pathway Zhongliu Fangzhi Yanjiu limonin jak2/stat3 signaling pathway non-small cell lung cancer malignant biological behavior |
| title | Influence of Limonin on Malignant Biological Behavior of Non-small Cell Lung Cancer Cells by Regulating JAK2/STAT3 Signaling Pathway |
| title_full | Influence of Limonin on Malignant Biological Behavior of Non-small Cell Lung Cancer Cells by Regulating JAK2/STAT3 Signaling Pathway |
| title_fullStr | Influence of Limonin on Malignant Biological Behavior of Non-small Cell Lung Cancer Cells by Regulating JAK2/STAT3 Signaling Pathway |
| title_full_unstemmed | Influence of Limonin on Malignant Biological Behavior of Non-small Cell Lung Cancer Cells by Regulating JAK2/STAT3 Signaling Pathway |
| title_short | Influence of Limonin on Malignant Biological Behavior of Non-small Cell Lung Cancer Cells by Regulating JAK2/STAT3 Signaling Pathway |
| title_sort | influence of limonin on malignant biological behavior of non small cell lung cancer cells by regulating jak2 stat3 signaling pathway |
| topic | limonin jak2/stat3 signaling pathway non-small cell lung cancer malignant biological behavior |
| url | http://www.zlfzyj.com/EN/10.3971/j.issn.1000-8578.2023.23.0399 |
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