Cell Biochemistry and Biophysics最新文献

{"title":"PMEPA1 Binds NEDD4L to Inhibit the Malignant Progression of Multiple Myeloma by Inactivating Wnt/β-Catenin Signaling.","authors":"Shanshan Hu, Xinfang Gao, Yan Zhu, Fangjing Shi, Li Huang","doi":"10.1007/s12013-025-01674-w","DOIUrl":"https://doi.org/10.1007/s12013-025-01674-w","url":null,"abstract":"<p><p>Multiple myeloma (MM) is an incurable hematological malignancy with increasing prevalence. Prostate transmembrane androgen inducible protein 1 (PMEPA1) is positively associated with overall survival in MM patients, but the exact functions and mechanisms of PMEPA1 in MM have yet to be elucidated. PMEPA1 and neural precursor cell-expressed developmentally downregulated gene 4L (NEDD4L) levels in MM cells were examined. In RPMI-8226 cells with PMEPA1 overexpression or/and NEDD4L knockdown, cell proliferation, cycle distribution and apoptosis were evaluated with the application of CCK-8, EDU staining and flow cytometry. The BioGrid website and HDOCK SERVER were applied for predicting the binding between PMEPA1 and NEDD4L, which was checked by co-immunoprecipitation. Besides, the levels of proteins associated with proliferation (Ki67 and PCNA), apoptosis (Bcl-2, Bax and cleaved caspase3) and Wnt/β-catenin signaling (β-catenin, c-Myc and cyclin D1) was detected with immunoblotting. Finally, LiCl, an activator of Wnt/β-catenin pathway, was employed to treat RPMI-8226 cells to analyze the proliferation, cycle distribution and apoptosis of MM cells. As a result, PMEPA1 and NEDD4L were expressed at low levels in MM cells. PMEPA1 upregulation repressed proliferation induced cycle arrest and facilitated apoptosis of MM cells. Moreover, PMEPA1 bound to NEDD4L and upregulated NEDD4L expression in RPMI-8226 cells. Functionally, NEDD4L knockdown attenuated the influences of PMEPA1 overexpression on the proliferation, cycle distribution and apoptosis of RPMI-8226 cells. Additionally, PMEPA1 notably downregulated β-catenin, c-Myc and cyclin D1 expression in RPMI-8226 cells, which was abrogated by NEDD4L silencing. Further adding LiCl in RPMI-8226 cells led to the enhanced malignant biological behaviors. Collectively, PMEPA1 damaged MM progression through binding NEDD4L to inactivate Wnt/β-catenin signaling, which may be helpful to develop promising targets for MM treatment.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperuricemia Facilitates Uric Acid-Mediated Vascular Endothelial Cell Damage by Inhibiting Mitophagy.","authors":"Gang Wu, Jun Liu, Guirong Ma, Qiuyu Wei, Xinghui Song","doi":"10.1007/s12013-024-01512-5","DOIUrl":"10.1007/s12013-024-01512-5","url":null,"abstract":"<p><p>Hyperuricemia remains an elusive factor in the pathogenesis of vascular endothelial injury. This study elucidates the role of hydroxychloroquine (HCQ) in the context of uric acid (UA)-induced vascular endothelial cell damage. Human umbilical vein endothelial cells (HUVECs) were exposed to varying UA concentrations (6 mg/dL to 50 mg/dL) for 48 h, or to 50 mg/dL UA for different time points (6 to 72 h). We observed a concentration- and time-dependent inhibition of cell proliferation, particularly at 40 mg/dL and 50 mg/dL UA. The autophagy marker LC3 exhibited reduced fluorescence intensity post-UA treatment, along with decreased expression of LC3-II/LC3I, beclin1, and p62, indicating impaired autophagy. The mechanistic exploration revealed that HCQ, in conjunction with the mitochondrial autophagy inhibitor Cyclosporine A (CsA), exacerbated the inhibitory effects of UA on HUVEC autophagy. This was evidenced by a further reduction in mitochondrial autophagy-related proteins and diminished fluorescence of LC3-II/LC3-I and Parkin, culminating in suppressed cell proliferation and accelerated cell senescence and apoptosis. Conversely, the co-treatment with the mitochondrial autophagy inducer carbonyl cyanide m-chlorophenyl hydrazine (CCCP) and HCQ mitigated the detrimental effects of UA on HUVEC autophagy. This intervention led to increased expression of PINK1, Parkin, Bnip3, and Nix, along with enhanced fluorescence of LC3-II/LC3-I and Parkin, effectively inhibiting cell senescence and apoptosis while promoting cell proliferation. In conclusion, our findings underscore the pivotal role of HCQ in modulating UA-mediated vascular endothelial cell damage through the inhibition of mitophagy, providing novel insights into the therapeutic potential of targeting HCQ in the management of hyperuricemia-associated vascular complications.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"811-821"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Investigation on Optical, Larvacidal and Cytotoxicity Analysis of Sulfanilic Acid Single Crystal for Optical and Biomedical Applications.","authors":"Punithavathi Manogaran, Thirupathy Jayapalan, Revathi Palanisamy","doi":"10.1007/s12013-024-01547-8","DOIUrl":"10.1007/s12013-024-01547-8","url":null,"abstract":"<p><p>Sulfanilic acid (SFA) crystal is well known as an effective material for photonic, electro-optical, harmonic generating and biomedical applications. A well-known nonlinear optical material, a high-quality SFA single crystal made utilizing the slow evaporation solution method (SEST) is the subject of this article. A 75 days development period yielded a transparent SFA single crystal measuring 5 × 5 × 2 mm³. The grown crystal used for different characterizations like Single crystal XRD used to find out the cell parameters. Fourier transforms infrared utilized to identify the band assignments. UV-Visible analysis used to detect the absorbance of the crystal and it is utilized for optical application. Photoluminescence studies utilized to recognize the excitation and emission of the grown crystal. Fluorescence used for determining the crystallinity and purity of the sample. The quantitative analysis is verified by using Elemental Dispersive Analysis by X-Rays. Scanning Electron Microscopy utilized to identify the structural and morphological characteristics. To the best of our knowledge, this paper is the first to provide the generated crystal that was used to analyze cytotoxicity and larvacidal activity. Assessment of larvicidal activity was used to ascertain the anti-malarial efficacy. We tested the items on MCF7-Human Breast cancer cell line and MCF7 Vero cells using the MTT Assay to identify the molecular basis of their cytotoxicity in vitro. Biological and optical are two areas that could benefit from the created crystal.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"1139-1149"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Regulation of Epidermal Growth Factor and Hormonal Receptors by Kinase Inhibitors and Organofluorines in Breast Cancer Therapy.","authors":"Jitender Singh, Krishan Lal Khanduja, Divya Dahiya, Pramod K Avti","doi":"10.1007/s12013-024-01546-9","DOIUrl":"10.1007/s12013-024-01546-9","url":null,"abstract":"<p><p>Differential expression patterns of growth factor (EGFR, HER-2) and hormonal (ER, PR) receptors in breast cancer (BC) remain crucial for evaluating and tailoring therapeutic interventions. This study investigates differential expression profiles of hormonal and growth factor receptors in BC patients and across age groups, major subclasses, disease stages and tumor histology and survival rates, the efficacy of emerging clinical trial drugs (Dabrafenib and Palbociclib) and elucidating their molecular interaction mechanisms for efficient therapeutic strategies. Gene and protein expression analysis in the normal vs BC and across age groups and major subclasses reveals divergent patterns as EGFR and HER-2 levels are reduced in tumors versus normal tissue, while ER and PR levels are higher, particularly in luminal subtypes. However, there was no significant difference in survival rates among high and low/medium expression levels of EGFR and PR receptors. Conversely, patients with high HER-2 and ER expression exhibited poorer survival rates compared to low or medium expression levels. The in vitro findings indicate that Dabrafenib exhibits greater effectiveness than Palbociclib in suppressing various BC cells such as MCF-7 (Luminal), MDA-MB-231 (Triple-Negative), SKBR-3 (HER-2 + ) proliferation, promoting cell death, (IC₅₀ of Dab < Pal) at 24 and 48 h, ROS production, and reduced ER and PR, elevated HER-2 with no change in EGFR expression. Molecular simulation studies revealed Dabrafenib's thermodynamically stable interactions (ΔG), tighter binding, and less structural deviation in the order EGFR > HER-2 > ER > PR as compared to Palbociclib (HER-2 > ER > PR = EGFR). These results indicate that Dabrafenib, compared to Palbociclib, more effectively regulates breast cancer cell proliferation through specific interactions with hormonal and growth factor receptors towards a repurposing approach.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"1113-1137"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: In Silico Investigation against Inhibitors of Alpha-Amylase Using Structure-based Screening, Molecular Docking, and Molecular Simulations Studies.","authors":"Fariya Khan, Altaf Ahmad Shah, Ajay Kumar, Salman Akhtar","doi":"10.1007/s12013-024-01490-8","DOIUrl":"10.1007/s12013-024-01490-8","url":null,"abstract":"","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"1323"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chondrocyte Ferritinophagy as a Molecular Mechanism of Arthritis-A Narrative Review.","authors":"Yong Liu, Chao Song, Silong Gao, Daqian Zhou, Jiale Lv, Yang Zhou, Liquan Wang, Houyin Shi, Fei Liu, Zhongwei Xiong, Yunqing Hou, Zongchao Liu","doi":"10.1007/s12013-024-01534-z","DOIUrl":"10.1007/s12013-024-01534-z","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a prevalent joint disease affecting orthopedic patients. Its incidence is steadily increasing, causing great economic hardship for individuals and society as a whole. OA is connected with risk factors such as genetics, obesity, and joint diseases; yet, its pathophysiology is still largely understood. At present, several cell death pathways govern the initiation and advancement of OA. It has been discovered that the onset and progression of OA are strongly associated with pyroptosis, senescence, apoptosis, ferroptosis, and autophagy. Ferroptosis and autophagy have not been well studied in OA, and elucidating their molecular mechanisms in chondrocytes is important for the diagnosis of OA. For this reason, we aim was reviewed recent national and international developments and provided an initial understanding of the molecular pathways underlying autophagy and ferroptosis in OA. We determined the reference period to be the last five years by searching for the keywords \"osteoarthritis, mechanical stress, Pizeo1, ferroptosis, autophagy, ferritin autophagy\" in the three databases of PUBMED, Web of Science, Google Scholar. We then screened irrelevant literature by reading the abstracts. Ferroptosis is a type of programmed cell death that is dependent on reactive oxygen species and Fe²⁺. It is primarily caused by processes linked to amino acid metabolism, lipid peroxidation, and iron metabolism. Furthermore, Piezoelectric mechanically sensitive ion channel assembly 1 (PIEZO1), which is triggered by mechanical stress, has been revealed to be intimately associated with ferroptosis events. It was found that mechanical injury triggers changes in the intracellular environment of articular chondrocytes (e.g., elevated levels of oxidative stress and increased inflammation) through PIEZO1, ultimately leading to iron death in chondrocytes. Therefore, we believe that PIEZO1 is a key initiator protein of iron death in chondrocytes. Widely present in eukaryotic cells, autophagy is a lysosome-dependent, evolutionarily conserved catabolic process that carries misfolded proteins, damaged organelles, and other macromolecules to lysosomes for breakdown and recycling. Throughout OA, autophagy is activated to differing degrees, indicating that autophagy may play a role in the development of OA. According to recent research, autophagy is a major factor in the process that leads cells to ferroptosis. Despite the notion of ferritinophagy being put forth, not much research has been done to clarify the connection between ferroptosis and autophagy in OA.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"1021-1033"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SUV39H1 Regulates Gastric Cancer Progression via the H3K9me3/ALDOB Axis.","authors":"Xueyong Li, Cuixia Liu, Yi Gao","doi":"10.1007/s12013-024-01524-1","DOIUrl":"10.1007/s12013-024-01524-1","url":null,"abstract":"<p><p>Gastric cancer (GC) is a malignant tumor with high incidence rate. H3K9me3 is related to transcriptional suppression and modulated by histone methyltransferase suppressor of variegation 3-9 homolog 1 (SUV39H1). SUV39H1 is dysregulated in assorted cancers and exerts the regulatory function. Nevertheless, the specific biofunction of SUV39H1 in GC needs further confirmation. SUV39H1 and H3K9me3 expressions were tested through RT-qPCR and western blot. Colony formation, wound healing, and transwell assays were employed for testing cell behaviors. ChIP assay was utilized for assessing the interaction between H3K9me3 and aldolase B (ALDOB). Xenograft experiment was employed for measuring tumor growth. We found that SUV39H1 and H3K9me3 were overexpressed in GC tissues and cells. SUV39H1 knockdown notably suppressed GC cell proliferative, migratory, and invasive capabilities. The treatment of chaetocin or F5446 (inhibitors of SUV39H1 enzymatic activity) also restrained GC cell behaviors. In addition, we discovered that SUV39H1 could negatively regulate ALDOB expression. SUV39H1 depletion reduced H3K9me3 modification to ALDOB promoter region. In rescue assays, we proved that ALDOB reduction reversed the inhibitory functions of SUV39H1 silencing on GC progression. Furthermore, tumor growth of mice was suppressed by sh-SUV39H1 transfection, chaetocin treatment, or F5446 treatment. In conclusion, SUV39H1 promoted GC progression by modulating the H3K9me3/ALDOB axis.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"919-928"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cinnamaldehyde Alleviates Alveolar Epithelial Cell Injury in ALI by Inhibiting the CaMKII Pathway.","authors":"Lei Liu, Hao Zhang, Siming Chen, Wankang Dian, Zhou Zheng","doi":"10.1007/s12013-024-01544-x","DOIUrl":"10.1007/s12013-024-01544-x","url":null,"abstract":"<p><p>Alveolar epithelial cell injury plays a key role in acute lung injury (ALI) and is a vital determinant of its severity. Here, we aimed to assess the protective effects of cinnamaldehyde (CA) on lipopolysaccharide (LPS)-induced A549 cells and elucidate the underlying mechanisms. A549 cells were stimulated with 1 μg/mL LPS for 24 h to establish an alveolar epithelial cell injury model and subsequently treated with CA or Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN93. Flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, and lactate dehydrogenase release assays were used to evaluate apoptosis, cell viability, and lactate dehydrogenase activity, respectively. Levels of inflammatory cytokines (interleukin-6, interleukin-1β, tumor necrosis tactor-α, and interferon-γ) and oxidative stress markers (reactive oxygen species, superoxide dismutase, catalase, and malondialdehyde) were determined using enzyme-linked immunosorbent assay and specific assay kits, respectively. Furthermore, levels of apoptosis-related proteins (cleaved caspase-3, Bcl-2-associated X, and Bcl-2) and CaMKII were assessed via western blotting. CA did not exhibit significant cytotoxicity in A549 cells. It dose-dependently improved the cell viability, suppressed apoptosis, decreased cleaved caspase-3 and Bcl-2-associated X levels, and increased Bcl-2 levels in LPS-treated A549 cells. It also inhibited inflammatory factor release and oxidative stress in LPS-induced A549 cells. Similar results were observed in the KN93- and CA-treated groups. Western blotting assay revealed that CA and KN93 inhibited CaMKII pathway activation, as indicated by the reduced p-CaMKII and p-phospholamban (PLN) levels and p-CaMKII/CaMKII and p-PLN/PLN ratios. Overall, CA alleviated alveolar epithelial cell injury by inhibiting the inflammatory response and oxidative stress and inducing cell apoptosis in LPS-induced A549 cells by regulating the CaMKII pathway, serving as a potential candidate for ALI prevention and treatment.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"1097-1104"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic Bioactivity of Aegiceras corniculatum (L.) Blanco and Its Endophytic Fungus Aspergillus: Antioxidant, Antimicrobial, and Cytotoxic Effects.","authors":"Sharika Noshin, Rahul Dev Bairagi, Sadia Airin, Dipa Debnath, Md Sohanur Rahaman, Amit Kumar Acharzo, Most Nazmin Aktar, Mohammed Bourhia, Ahmad Mohammad Salamatullah, Md Amirul Islam","doi":"10.1007/s12013-024-01553-w","DOIUrl":"10.1007/s12013-024-01553-w","url":null,"abstract":"<p><p>The mangrove fungi provide a vast and unexplored source of diverse and unique chemicals and biological properties. The plant Aegiceras corniculatum (L.) Blanco and its endophytic fungus aspergillus species were collected from different sites of the Baleswar river region in Sundarban. Hence, we compared the antioxidant properties of the associated fungus ACSF-1 and the methanolic bark extract of Aegiceras corniculatum (MBAC) by measuring the total phenolic content (TPC), total flavonoid content (TFC), and DPPH free radical assay. Subsequently, antimicrobial activity was measured using the disc diffusion method, and cytotoxic activity was measured using the brine shrimp lethality bioassay. The results showed that MBAC has even more DPPH scavenging activity (IC₅₀ = 44.036 μg/mL), TPC (310.275 mg GAE/g), and TFC (66.275 mg QE/g) in comparison with DPPH scavenging activity (IC₅₀ = 92.542 μg/mL), TPC (234.832 mg GAE/g), and TFC (134.887 mg QE/g) in ACSF-1. The median lethal concentration value (LC₅₀) of MBAC and ACSF-1 was found to be 43.93 μg/mL and 336.84 μg/mL, respectively. Moreover, MBAC showed a dose-dependent antimicrobial response to Escherichia coli and Staphylococcus aureus, whereas ACSF-1 was found to have activity against Bacillus subtilis and S. aureus. These results emphasize the unique pharmacological characteristics of both the plant and fungus, indicating their potential usefulness in various therapeutic fields.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"1197-1206"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T-Box Transcription Factor 2 Mediates Chemoresistance of Endometrial Cancer via Regulating FSP1-involved Ferroptosis.","authors":"Xiaohui Yu, Xuemei Yao, Fangfang Song, Xiaolin Zhu","doi":"10.1007/s12013-024-01518-z","DOIUrl":"10.1007/s12013-024-01518-z","url":null,"abstract":"<p><p>Chemotherapy is increasingly being used in the first-line treatment of endometrial cancer (EC) patients. However, chemoresistance seriously affects its efficacy. Understanding the underlying molecular mechanisms is critical for EC treatment. We explored the regulatory role of T-Box transcription factor 2 (TBX2)-ferroptosis suppressor protein 1 (FSP1) axis in ferroptosis and chemoresistance of EC. Cisplatin-resistant cell line Ishikawa/DDP cells were utilized to generate TBX2 and FSP1 overexpression and knockdown stable cell lines by using lentivirus infection and puromycin selection. Cell viability and ferroptosis status were evaluated in EC cells with or without Cisplatin and/or FSP1 inhibitor (iFSP1) using CKK-8, lipid peroxidation, malondialdehyde, and lactate dehydrogenase release assays. Endometrial carcinoma xenograft mouse model was established to further explore the function of TBX2-FSP1 axis on ferroptosis and tumor progression in EC. TBX2 suppressed Cisplatin-induced ferroptosis through up-regulating FSP1 expression level in EC cells. On the contrary, knockdown of TBX2 reduced FSP1 expression and significantly promoted Cisplatin-induced ferroptosis. TBX2 or FSP1 overexpression and knockdown promote and inhibit EC tumor growth under Cisplatin treatment, respectively. Interestingly, silence FSP1 could reverse TBX2-mediated ferroptosis inhibition and tumor-promoting effect. TBX2-FSP1 axis inhibits ferroptosis and enhances the Cisplatin resistance, which will provide an important theoretical basis and potential solution for the clinical treatment of EC.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":"1313-1320"},"PeriodicalIF":1.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}