Endogenous IL-33 inhibits apoptosis in non-small cell lung cancer cells by regulating BCL2/BAX via the ERK1/2 pathway
Abstract Lung cancer remains a leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of cases. Although targeted therapies have improved treatment outcomes, drug resistance poses a significant challenge, underscoring the need for novel therap...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-91202-w |
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| author | Liping Liu Haoge Luo Yingdong Xie Ying Wang Shiying Ren Haiyang Sun Zhuoyuan Xin Dong Li |
| author_facet | Liping Liu Haoge Luo Yingdong Xie Ying Wang Shiying Ren Haiyang Sun Zhuoyuan Xin Dong Li |
| author_sort | Liping Liu |
| collection | DOAJ |
| description | Abstract Lung cancer remains a leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of cases. Although targeted therapies have improved treatment outcomes, drug resistance poses a significant challenge, underscoring the need for novel therapeutic strategies. Interleukin-33 (IL-33), a member of the IL-1 superfamily, functions both as a nuclear protein and a cytokine, binding to its receptor, ST2. While IL-33 is known to promote tumour cell migration and metastasis, its role in regulating apoptosis remains incompletely understood. In this study, we focused on endogenous IL-33, employing lentiviral transfection to overexpress both the full-length and mature forms of IL-33 in lung cancer cells. We examined its effects on apoptosis in vitro and investigated the underlying molecular mechanisms. Our findings reveal that endogenous IL-33 inhibits apoptosis in lung cancer cells by modulating the expression of BCL2 and BAX via the ERK1/2 pathway in an autocrine manner. These results uncover a novel mechanism of IL-33-mediated tumour survival and provide a foundation for the development of IL-33/ST2-targeted therapies in NSCLC. |
| format | Article |
| id | doaj-art-05b33dfdf5144c1a944d01e830e24433 |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-05b33dfdf5144c1a944d01e830e244332025-08-20T03:11:07ZengNature PortfolioScientific Reports2045-23222025-02-0115111210.1038/s41598-025-91202-wEndogenous IL-33 inhibits apoptosis in non-small cell lung cancer cells by regulating BCL2/BAX via the ERK1/2 pathwayLiping Liu0Haoge Luo1Yingdong Xie2Ying Wang3Shiying Ren4Haiyang Sun5Zhuoyuan Xin6Dong Li7Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin UniversityKey Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin UniversityKey Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin UniversityKey Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin UniversityKey Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin UniversityKey Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin UniversityKey Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin UniversityKey Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin UniversityAbstract Lung cancer remains a leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of cases. Although targeted therapies have improved treatment outcomes, drug resistance poses a significant challenge, underscoring the need for novel therapeutic strategies. Interleukin-33 (IL-33), a member of the IL-1 superfamily, functions both as a nuclear protein and a cytokine, binding to its receptor, ST2. While IL-33 is known to promote tumour cell migration and metastasis, its role in regulating apoptosis remains incompletely understood. In this study, we focused on endogenous IL-33, employing lentiviral transfection to overexpress both the full-length and mature forms of IL-33 in lung cancer cells. We examined its effects on apoptosis in vitro and investigated the underlying molecular mechanisms. Our findings reveal that endogenous IL-33 inhibits apoptosis in lung cancer cells by modulating the expression of BCL2 and BAX via the ERK1/2 pathway in an autocrine manner. These results uncover a novel mechanism of IL-33-mediated tumour survival and provide a foundation for the development of IL-33/ST2-targeted therapies in NSCLC.https://doi.org/10.1038/s41598-025-91202-wIL-33ST2Non-small-cell lung cancerApoptosis |
| spellingShingle | Liping Liu Haoge Luo Yingdong Xie Ying Wang Shiying Ren Haiyang Sun Zhuoyuan Xin Dong Li Endogenous IL-33 inhibits apoptosis in non-small cell lung cancer cells by regulating BCL2/BAX via the ERK1/2 pathway Scientific Reports IL-33 ST2 Non-small-cell lung cancer Apoptosis |
| title | Endogenous IL-33 inhibits apoptosis in non-small cell lung cancer cells by regulating BCL2/BAX via the ERK1/2 pathway |
| title_full | Endogenous IL-33 inhibits apoptosis in non-small cell lung cancer cells by regulating BCL2/BAX via the ERK1/2 pathway |
| title_fullStr | Endogenous IL-33 inhibits apoptosis in non-small cell lung cancer cells by regulating BCL2/BAX via the ERK1/2 pathway |
| title_full_unstemmed | Endogenous IL-33 inhibits apoptosis in non-small cell lung cancer cells by regulating BCL2/BAX via the ERK1/2 pathway |
| title_short | Endogenous IL-33 inhibits apoptosis in non-small cell lung cancer cells by regulating BCL2/BAX via the ERK1/2 pathway |
| title_sort | endogenous il 33 inhibits apoptosis in non small cell lung cancer cells by regulating bcl2 bax via the erk1 2 pathway |
| topic | IL-33 ST2 Non-small-cell lung cancer Apoptosis |
| url | https://doi.org/10.1038/s41598-025-91202-w |
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