A research on the mechanism of SERPINA3 promoting malignant progression and gemcitabine resistance of pancreatic cancer by inhibiting ferroptosis
Background and purpose: Members of the serine protease inhibitor (SERPIN) family can influence tumorigenesis, progression, and prognosis by modulating processes such as apoptosis, invasion, metastasis, and angiogenesis in tumor cells. However, their role in pancreatic cancer remains unclear. This st...
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Editorial Office of China Oncology
2025-06-01
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| Series: | Zhongguo aizheng zazhi |
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| Online Access: | https://www.china-oncology.com/fileup/1007-3639/PDF/1752457546615-510644080.pdf |
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| author | HE Yuan, GUO Juncheng, YE Zhibin, WANG Xiaohu, LI Haonan, HUANG Jingbiao |
| author_facet | HE Yuan, GUO Juncheng, YE Zhibin, WANG Xiaohu, LI Haonan, HUANG Jingbiao |
| author_sort | HE Yuan, GUO Juncheng, YE Zhibin, WANG Xiaohu, LI Haonan, HUANG Jingbiao |
| collection | DOAJ |
| description | Background and purpose: Members of the serine protease inhibitor (SERPIN) family can influence tumorigenesis, progression, and prognosis by modulating processes such as apoptosis, invasion, metastasis, and angiogenesis in tumor cells. However, their role in pancreatic cancer remains unclear. This study aimed to investigate the impact of high expression of serine protease inhibitor A3 (SERPINA3) on the proliferation, apoptosis, migration, and chemoresistance of pancreatic cancer cells and its mechanism. Methods: This study analyzed the SERPINA3 expression levels in the normal pancreatic ductal epithelial cell line hTERT-HPNE and pancreatic cancer cell lines SW1990, Capan-1, PANC-1, and ASPC-1 by real-time reverse transcription quantitative polymerase chain reaction (qRT-PCR). We established gemcitabine-resistant pancreatic cancer cell lines PANC-1/R and ASPC-1/R, and used qRT-PCR assay and cell counting kit-8 (CCK-8) to determine the SERPINA3 expression levels in the constructed resistant cell lines and their parental sensitive cell lines, as well as the differences in their chemosensitivity to gemcitabine. We constructed the SERPINA3-knockdown cell line si-SERPINA with siRNA, and the negative control group si-SERPINA#NC with siRNA negative control. We used MDA assay, CCK-8 assay, EdU cell proliferation assay, transwell migration assay, matrigel invasion assay, scratch assay, and apoptotic assay to respectively detect the lipid oxidation levels, proliferation, migration, invasion, wound-healing ability, and the influence on apoptosis of the gemcitabine-resistant pancreatic cancer cells in the si-SERPINA group and the si-SERPINA#NC group. Results: Compared with normal pancreatic ductal epithelial cells hTERT-HPNE, the expression level of SERPINA3 in various pancreatic cancer cell lines was significantly increased (P<0.05). mRNA and protein expression levels of SERPINA3 in PANC-1/R and ASPC-1/R were significantly increased compared with those in parent cells (P<0.001). When SERPINA3 was knocked down in PANC-1/R and ASPC-1/R cells, the survival rate of the cells under different concentrations of gemcitabine chemotherapy decreased, and MDA detected that the lipid oxidation level was increased (P<0.001). In addition, the proliferation rate of PANC-1/R and ASPC-1/R cell lines with SERPINA3 knockout, the number of migrating/invading cells and the healing rate of scratch test were significantly decreased (P<0.01), and flow cytometry demonstrated that the number of apoptotic cells was increased (P<0.05). These results suggest that SERPINA3 knockdown can inhibit the proliferation, migration, invasion and wound healing ability of gemcitabine-resistant pancreatic cancer cells, and promote the apoptosis of these resistant cells. Conclusion: SERPINA3 overexpression was found in various pancreatic cancer cells. SERPINA3 overexpression promoted malignant progression and chemotherapy resistance of pancreatic cancer, and interference with SERPINA3 expression promoted ferroptosis and enhanced chemotherapy sensitivity of gemcitabine-resistant pancreatic cancer cells. |
| format | Article |
| id | doaj-art-22250e848a1c42398a52050c6db2fe64 |
| institution | OA Journals |
| issn | 1007-3639 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Editorial Office of China Oncology |
| record_format | Article |
| series | Zhongguo aizheng zazhi |
| spelling | doaj-art-22250e848a1c42398a52050c6db2fe642025-08-20T02:37:04ZengEditorial Office of China OncologyZhongguo aizheng zazhi1007-36392025-06-0135655556210.19401/j.cnki.1007-3639.2025.06.004A research on the mechanism of SERPINA3 promoting malignant progression and gemcitabine resistance of pancreatic cancer by inhibiting ferroptosisHE Yuan, GUO Juncheng, YE Zhibin, WANG Xiaohu, LI Haonan, HUANG Jingbiao01. Department of Gastrointestial Surgery, Heping Hospital Affiliated to Changzhi Medical College, Changzhi 046000, Shanxi Province, China;2. The First Clinical College of Changzhi Medical College, Changzhi 046000, Shanxi Province, China;3. Department of Gastrointestial Surgery, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, ChinaBackground and purpose: Members of the serine protease inhibitor (SERPIN) family can influence tumorigenesis, progression, and prognosis by modulating processes such as apoptosis, invasion, metastasis, and angiogenesis in tumor cells. However, their role in pancreatic cancer remains unclear. This study aimed to investigate the impact of high expression of serine protease inhibitor A3 (SERPINA3) on the proliferation, apoptosis, migration, and chemoresistance of pancreatic cancer cells and its mechanism. Methods: This study analyzed the SERPINA3 expression levels in the normal pancreatic ductal epithelial cell line hTERT-HPNE and pancreatic cancer cell lines SW1990, Capan-1, PANC-1, and ASPC-1 by real-time reverse transcription quantitative polymerase chain reaction (qRT-PCR). We established gemcitabine-resistant pancreatic cancer cell lines PANC-1/R and ASPC-1/R, and used qRT-PCR assay and cell counting kit-8 (CCK-8) to determine the SERPINA3 expression levels in the constructed resistant cell lines and their parental sensitive cell lines, as well as the differences in their chemosensitivity to gemcitabine. We constructed the SERPINA3-knockdown cell line si-SERPINA with siRNA, and the negative control group si-SERPINA#NC with siRNA negative control. We used MDA assay, CCK-8 assay, EdU cell proliferation assay, transwell migration assay, matrigel invasion assay, scratch assay, and apoptotic assay to respectively detect the lipid oxidation levels, proliferation, migration, invasion, wound-healing ability, and the influence on apoptosis of the gemcitabine-resistant pancreatic cancer cells in the si-SERPINA group and the si-SERPINA#NC group. Results: Compared with normal pancreatic ductal epithelial cells hTERT-HPNE, the expression level of SERPINA3 in various pancreatic cancer cell lines was significantly increased (P<0.05). mRNA and protein expression levels of SERPINA3 in PANC-1/R and ASPC-1/R were significantly increased compared with those in parent cells (P<0.001). When SERPINA3 was knocked down in PANC-1/R and ASPC-1/R cells, the survival rate of the cells under different concentrations of gemcitabine chemotherapy decreased, and MDA detected that the lipid oxidation level was increased (P<0.001). In addition, the proliferation rate of PANC-1/R and ASPC-1/R cell lines with SERPINA3 knockout, the number of migrating/invading cells and the healing rate of scratch test were significantly decreased (P<0.01), and flow cytometry demonstrated that the number of apoptotic cells was increased (P<0.05). These results suggest that SERPINA3 knockdown can inhibit the proliferation, migration, invasion and wound healing ability of gemcitabine-resistant pancreatic cancer cells, and promote the apoptosis of these resistant cells. Conclusion: SERPINA3 overexpression was found in various pancreatic cancer cells. SERPINA3 overexpression promoted malignant progression and chemotherapy resistance of pancreatic cancer, and interference with SERPINA3 expression promoted ferroptosis and enhanced chemotherapy sensitivity of gemcitabine-resistant pancreatic cancer cells.https://www.china-oncology.com/fileup/1007-3639/PDF/1752457546615-510644080.pdf|pancreatic cancer|serpina3|ferroptosis|gemcitabine|drug resistance |
| spellingShingle | HE Yuan, GUO Juncheng, YE Zhibin, WANG Xiaohu, LI Haonan, HUANG Jingbiao A research on the mechanism of SERPINA3 promoting malignant progression and gemcitabine resistance of pancreatic cancer by inhibiting ferroptosis Zhongguo aizheng zazhi |pancreatic cancer|serpina3|ferroptosis|gemcitabine|drug resistance |
| title | A research on the mechanism of SERPINA3 promoting malignant progression and gemcitabine resistance of pancreatic cancer by inhibiting ferroptosis |
| title_full | A research on the mechanism of SERPINA3 promoting malignant progression and gemcitabine resistance of pancreatic cancer by inhibiting ferroptosis |
| title_fullStr | A research on the mechanism of SERPINA3 promoting malignant progression and gemcitabine resistance of pancreatic cancer by inhibiting ferroptosis |
| title_full_unstemmed | A research on the mechanism of SERPINA3 promoting malignant progression and gemcitabine resistance of pancreatic cancer by inhibiting ferroptosis |
| title_short | A research on the mechanism of SERPINA3 promoting malignant progression and gemcitabine resistance of pancreatic cancer by inhibiting ferroptosis |
| title_sort | research on the mechanism of serpina3 promoting malignant progression and gemcitabine resistance of pancreatic cancer by inhibiting ferroptosis |
| topic | |pancreatic cancer|serpina3|ferroptosis|gemcitabine|drug resistance |
| url | https://www.china-oncology.com/fileup/1007-3639/PDF/1752457546615-510644080.pdf |
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