Knockdown of SLC7A5 inhibits malignant progression and attenuates oxaliplatin resistance in gastric cancer by suppressing glycolysis
Abstract Background Chemotherapy resistance is a major challenge in the treatment of intermediate and advanced gastric cancer (GC). This study aimed to recognize oxaliplatin resistance-related genes (OXARGs) in GC and to explore their role and mechanism in oxaliplatin resistance of GC. Methods OXARG...
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BMC
2025-03-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-025-01175-9 |
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| author | Yan Zhang Jian Cao Zheng Yuan Jiahui Zhou Hao Zuo Xinsheng Miao Xinhua Gu |
| author_facet | Yan Zhang Jian Cao Zheng Yuan Jiahui Zhou Hao Zuo Xinsheng Miao Xinhua Gu |
| author_sort | Yan Zhang |
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| description | Abstract Background Chemotherapy resistance is a major challenge in the treatment of intermediate and advanced gastric cancer (GC). This study aimed to recognize oxaliplatin resistance-related genes (OXARGs) in GC and to explore their role and mechanism in oxaliplatin resistance of GC. Methods OXARGs with prognostic value in GC were analyzed using GC oxaliplatin resistance data from the GEO and TCGA databases. RT-qPCR and WB assay were applied to verify the expression of MT2A, NOTCH1 and SLC7A5 in oxaliplatin-resistant GC cells (HGC27R and MKN45R). The effect of SLC7A5 on the malignant phenotype of oxaliplatin-resistant GC cells was verified by CCK-8, EDU, TUNEL, colony formation, wound healing, transwell assay, tumor bearing experiments and WB assay. Results Bioinformatics analysis and experimental validation indicate that SLC7A5 was a target for oxaliplatin-resistance in GC. Knockdown of SLC7A5 obviously decreased the viability, migration, and invasion of oxaliplatin-resistant GC cells in vitro and tumor growth in vivo. It also increased the apoptosis levels and BAX expression, and reduced the expression of BCL2, MMP 2 and MMP9. Additionally, the knockdown of SLC7A5 enhanced the sensitivity of oxaliplatin-resistant GC cells to oxaliplatin both in vitro and in vivo. Furthermore, knockdown of SLC7A5 downregulated the expression of HK2, LDHA, Glut1, and PDK1 both in vivo and in vitro, leading to increased extracellular glucose levels and decreased lactate levels. However, glutathione significantly attenuated the regulatory effect of SLC7A5 knockdown on the malignant phenotype of oxaliplatin-resistant GC cells. Trial registration Not Applicable. Conclusion Knockdown of SLC7A5 inhibits malignant progression and attenuates oxaliplatin resistance in GC by suppressing glycolysis. |
| format | Article |
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| institution | Kabale University |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
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| series | Molecular Medicine |
| spelling | doaj-art-d2de99d88592453d9f35b6d615c32c642025-08-20T03:40:50ZengBMCMolecular Medicine1528-36582025-03-0131112210.1186/s10020-025-01175-9Knockdown of SLC7A5 inhibits malignant progression and attenuates oxaliplatin resistance in gastric cancer by suppressing glycolysisYan Zhang0Jian Cao1Zheng Yuan2Jiahui Zhou3Hao Zuo4Xinsheng Miao5Xinhua Gu6Department of Gastrointestinal Surgery, Suzhou Municipal Hospital, Suzhou Hospital Affiliated to Gusu School of Nanjing Medical UniversityDepartment of Gastroenterology, Suzhou Municipal Hospital, Suzhou Hospital Affiliated to Gusu School of Nanjing Medical UniversityDepartment of Gastrointestinal Surgery, Suzhou Municipal Hospital, Suzhou Hospital Affiliated to Gusu School of Nanjing Medical UniversityDepartment of Gastrointestinal Surgery, Suzhou Municipal Hospital, Suzhou Hospital Affiliated to Gusu School of Nanjing Medical UniversityDepartment of Gastrointestinal Surgery, Suzhou Municipal Hospital, Suzhou Hospital Affiliated to Gusu School of Nanjing Medical UniversityDepartment of Gastrointestinal Surgery, Suzhou Municipal Hospital, Suzhou Hospital Affiliated to Gusu School of Nanjing Medical UniversityDepartment of Gastrointestinal Surgery, Suzhou Municipal Hospital, Suzhou Hospital Affiliated to Gusu School of Nanjing Medical UniversityAbstract Background Chemotherapy resistance is a major challenge in the treatment of intermediate and advanced gastric cancer (GC). This study aimed to recognize oxaliplatin resistance-related genes (OXARGs) in GC and to explore their role and mechanism in oxaliplatin resistance of GC. Methods OXARGs with prognostic value in GC were analyzed using GC oxaliplatin resistance data from the GEO and TCGA databases. RT-qPCR and WB assay were applied to verify the expression of MT2A, NOTCH1 and SLC7A5 in oxaliplatin-resistant GC cells (HGC27R and MKN45R). The effect of SLC7A5 on the malignant phenotype of oxaliplatin-resistant GC cells was verified by CCK-8, EDU, TUNEL, colony formation, wound healing, transwell assay, tumor bearing experiments and WB assay. Results Bioinformatics analysis and experimental validation indicate that SLC7A5 was a target for oxaliplatin-resistance in GC. Knockdown of SLC7A5 obviously decreased the viability, migration, and invasion of oxaliplatin-resistant GC cells in vitro and tumor growth in vivo. It also increased the apoptosis levels and BAX expression, and reduced the expression of BCL2, MMP 2 and MMP9. Additionally, the knockdown of SLC7A5 enhanced the sensitivity of oxaliplatin-resistant GC cells to oxaliplatin both in vitro and in vivo. Furthermore, knockdown of SLC7A5 downregulated the expression of HK2, LDHA, Glut1, and PDK1 both in vivo and in vitro, leading to increased extracellular glucose levels and decreased lactate levels. However, glutathione significantly attenuated the regulatory effect of SLC7A5 knockdown on the malignant phenotype of oxaliplatin-resistant GC cells. Trial registration Not Applicable. Conclusion Knockdown of SLC7A5 inhibits malignant progression and attenuates oxaliplatin resistance in GC by suppressing glycolysis.https://doi.org/10.1186/s10020-025-01175-9Gastric cancerOxaliplatin resistanceSLC7A5GlycolysisBioinformatics |
| spellingShingle | Yan Zhang Jian Cao Zheng Yuan Jiahui Zhou Hao Zuo Xinsheng Miao Xinhua Gu Knockdown of SLC7A5 inhibits malignant progression and attenuates oxaliplatin resistance in gastric cancer by suppressing glycolysis Molecular Medicine Gastric cancer Oxaliplatin resistance SLC7A5 Glycolysis Bioinformatics |
| title | Knockdown of SLC7A5 inhibits malignant progression and attenuates oxaliplatin resistance in gastric cancer by suppressing glycolysis |
| title_full | Knockdown of SLC7A5 inhibits malignant progression and attenuates oxaliplatin resistance in gastric cancer by suppressing glycolysis |
| title_fullStr | Knockdown of SLC7A5 inhibits malignant progression and attenuates oxaliplatin resistance in gastric cancer by suppressing glycolysis |
| title_full_unstemmed | Knockdown of SLC7A5 inhibits malignant progression and attenuates oxaliplatin resistance in gastric cancer by suppressing glycolysis |
| title_short | Knockdown of SLC7A5 inhibits malignant progression and attenuates oxaliplatin resistance in gastric cancer by suppressing glycolysis |
| title_sort | knockdown of slc7a5 inhibits malignant progression and attenuates oxaliplatin resistance in gastric cancer by suppressing glycolysis |
| topic | Gastric cancer Oxaliplatin resistance SLC7A5 Glycolysis Bioinformatics |
| url | https://doi.org/10.1186/s10020-025-01175-9 |
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