Tumor-associated macrophage-derived exosome miR-194 confers cisplatin resistance in GC cells
Abstract Objective At all stages of gastric cancer (GC), cisplatin is the first-line chemotherapeutic agent, but its efficacy remains limited, with a response rate of less than 20%, largely because of resistance to the drug. It aims to determine whether macrophage-derived exosomes are involved in th...
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| Format: | Article |
| Language: | English |
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BMC
2025-02-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-025-02329-5 |
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| author | Yi Zhou Yang-cheng Sun Qiong-yan Zhang Jing Wang Xian-ya Zhu Xiang-yu Su |
| author_facet | Yi Zhou Yang-cheng Sun Qiong-yan Zhang Jing Wang Xian-ya Zhu Xiang-yu Su |
| author_sort | Yi Zhou |
| collection | DOAJ |
| description | Abstract Objective At all stages of gastric cancer (GC), cisplatin is the first-line chemotherapeutic agent, but its efficacy remains limited, with a response rate of less than 20%, largely because of resistance to the drug. It aims to determine whether macrophage-derived exosomes are involved in the mechanism of cisplatin resistance, in order to identify potential methods for reversing resistance and improving patient outcomes. Methods Macrophages induced by IL-13 and IL-4 were characterized using flow cytometry, then co-cultured with GC cells and cisplatin. Cell viability and apoptosis were subsequently evaluated through CCK-8 assays and flow cytometry. Exosome miR-194, derived from M2 macrophages, was characterized and co-cultured with gastric cancer cells and cisplatin to assess cell survival. Furthermore, a mouse GC model was established, and miR-194 was injected to observe tumor growth. Results Results indicate that M2 macrophages enhance cisplatin resistance in gastric cancer cells mainly through miR-194, as demonstrated by CCK-8 and apoptosis assays. Cellular uptake experiments demonstrated that miR-194 can transfer from macrophages to GC cells and exert functional effects. Western blotting and PCR analysis further confirmed that macrophage-derived miR-194 inhibits apoptosis in GC cells and enhances cisplatin resistance by downregulating PTEN. Conclusion Macrophage-derived miR-194 promotes cisplatin resistance in GC cells by inhibiting apoptosis through PTEN downregulation. These findings provide new insights and theoretical backing for clinical treatment strategies in GC. |
| format | Article |
| id | doaj-art-45795f8c360b413c8d586a5d55221215 |
| institution | Kabale University |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-45795f8c360b413c8d586a5d552212152025-02-09T12:26:35ZengBMCEuropean Journal of Medical Research2047-783X2025-02-013011910.1186/s40001-025-02329-5Tumor-associated macrophage-derived exosome miR-194 confers cisplatin resistance in GC cellsYi Zhou0Yang-cheng Sun1Qiong-yan Zhang2Jing Wang3Xian-ya Zhu4Xiang-yu Su5Department of Hematology and Oncology, Wuzhong People’s HospitalDepartment of Hematology and Oncology, Wuzhong People’s HospitalDepartment of Hematology and Oncology, Wuzhong People’s HospitalDepartment of Hematology and Oncology, Wuzhong People’s HospitalDepartment of Hematology and Oncology, Wuzhong People’s HospitalDepartment of Oncology, School of Medicine, Zhongda Hospital, Southeast UniversityAbstract Objective At all stages of gastric cancer (GC), cisplatin is the first-line chemotherapeutic agent, but its efficacy remains limited, with a response rate of less than 20%, largely because of resistance to the drug. It aims to determine whether macrophage-derived exosomes are involved in the mechanism of cisplatin resistance, in order to identify potential methods for reversing resistance and improving patient outcomes. Methods Macrophages induced by IL-13 and IL-4 were characterized using flow cytometry, then co-cultured with GC cells and cisplatin. Cell viability and apoptosis were subsequently evaluated through CCK-8 assays and flow cytometry. Exosome miR-194, derived from M2 macrophages, was characterized and co-cultured with gastric cancer cells and cisplatin to assess cell survival. Furthermore, a mouse GC model was established, and miR-194 was injected to observe tumor growth. Results Results indicate that M2 macrophages enhance cisplatin resistance in gastric cancer cells mainly through miR-194, as demonstrated by CCK-8 and apoptosis assays. Cellular uptake experiments demonstrated that miR-194 can transfer from macrophages to GC cells and exert functional effects. Western blotting and PCR analysis further confirmed that macrophage-derived miR-194 inhibits apoptosis in GC cells and enhances cisplatin resistance by downregulating PTEN. Conclusion Macrophage-derived miR-194 promotes cisplatin resistance in GC cells by inhibiting apoptosis through PTEN downregulation. These findings provide new insights and theoretical backing for clinical treatment strategies in GC.https://doi.org/10.1186/s40001-025-02329-5Gastric cancermiR-194MacrophageCisplatin resistanceApoptosis |
| spellingShingle | Yi Zhou Yang-cheng Sun Qiong-yan Zhang Jing Wang Xian-ya Zhu Xiang-yu Su Tumor-associated macrophage-derived exosome miR-194 confers cisplatin resistance in GC cells European Journal of Medical Research Gastric cancer miR-194 Macrophage Cisplatin resistance Apoptosis |
| title | Tumor-associated macrophage-derived exosome miR-194 confers cisplatin resistance in GC cells |
| title_full | Tumor-associated macrophage-derived exosome miR-194 confers cisplatin resistance in GC cells |
| title_fullStr | Tumor-associated macrophage-derived exosome miR-194 confers cisplatin resistance in GC cells |
| title_full_unstemmed | Tumor-associated macrophage-derived exosome miR-194 confers cisplatin resistance in GC cells |
| title_short | Tumor-associated macrophage-derived exosome miR-194 confers cisplatin resistance in GC cells |
| title_sort | tumor associated macrophage derived exosome mir 194 confers cisplatin resistance in gc cells |
| topic | Gastric cancer miR-194 Macrophage Cisplatin resistance Apoptosis |
| url | https://doi.org/10.1186/s40001-025-02329-5 |
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